A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study Evaluating the Safety and Efficacy of Conestat Alfa As a Treatment for Angiotensin-Converting Enzyme-Inhibitor-Induced Angioedema

Angiotensin-converting enzyme inhibitors (ACE-Is), prescribed most often to treat hypertension, have been used extensively since the 1980s. Additional indications for their use include heart failure, diabetes mellitus, chronic kidney disease, and post-myocardial infarction. It is estimated that up to 40 million patients take ACE-Is worldwide. C1-INH is a serine protease inhibitor that is normally found in the blood. Its primary function is the regulation of the complement and contact system pathways by binding irreversibly to target proteases. It additionally inhibits the fibrinolytic, clotting, and kinin pathways.31 Patients with the hereditary forms of AE (HAE) tend to have lower quantitative or functional levels of C1-INH. This results in decreased suppression of plasma kallikrein and factor XIIa leading to cleavage of high molecular weight kininogen to form increased circulating levels of bradykinin. Bradykinin binds to bradykinin 2 receptors resulting in separation of endothelial vascular cells and extravasation of fluid manifesting clinically as angioedema. Conestat alfa (Ruconest®) is a recombinant human C1-INH that has been purified from the breast milk of genetically modified rabbits. It is a single-chain soluble glycoprotein that is made of 478 amino acids. Administering conestat alfa increases the amount of C1-INH in these patients, repleting their levels, and acting as a treatment for AE due to C1-INH deficiency. Conestat alfa has been studied on asymptomatic patients with HAE and was shown to dose-dependently increase the level of functional C1-INH. Additionally, it was shown to restore the level of the complement C4 protein, which is also decreased in these patients. Since the same pathophysiological pathway is involved in patients with ACE-I-induced AE, it is reasonable to hypothesize its effectiveness in the treatment of patients with acute attacks.

开始日期2024-12-01

申办/合作机构

University of Maryland

NCT05145283

/ Completed临床2期IIT

Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Acute Ischemic Cerebral and Renal Events After Transcatheter Aortic Valve Implantation: a Multi-center, Randomized, Double-blind, Placebo-controlled Investigational Study (PAIR-TAVI).

The aim of this trial is to assess the safety and efficacy of conestat alfa (Ruconest®, Pharming Technologies B.V.) on renal and cerebral ischemic events in patients undergoing TAVI for severe symptomatic aortic stenosis (AS) compared to placebo.

开始日期2022-03-16

申办/合作机构

Universitätsspital Basel

[+2]

NCT04912141

/ Terminated临床2期

Conestat Alfa (a Recombinant Human C1 Esterase Inhibitor) for the Prevention of Acute Kidney Injury After Non-ST Elevation Myocardial Infarction: a Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2, Dose-finding Study

A randomized, double-blind, placebo-controlled, multi-center, phase 2 clinical study in patients with NSTEMI undergoing urgent coronary angiography. Approximately 220 patients with CKD and acute NSTEMI, who are scheduled for an urgent coronary angiography (within 72 hours after admission and/or diagnosis of NSTEMI).

开始日期2021-04-21

申办/合作机构

Pharming Technologies BV

100 项与 Conestat alfa 相关的临床结果

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100 项与 Conestat alfa 相关的转化医学

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100 项与 Conestat alfa 相关的专利（医药）

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项与 Conestat alfa 相关的文献（医药）

2026-09-01·The journal of allergy and clinical immunology. Global

Sebetralstat for breakthrough attacks in patients with hereditary angioedema receiving long-term prophylaxis in KONFIDENT-S

Article

作者: Melamed, Isaac ; Farkas, Henriette ; Yea, Christopher M ; Bajcic, Paolo ; Honda, Daisuke ; Ohmura, Kazumasa ; Bouillet, Laurence ; Martinez-Saguer, Inmaculada ; Riedl, Marc A ; Kiani-Alikhan, Sorena ; Cancian, Mauro ; Zanichelli, Andrea ; Geng, Bob ; Bara, Noemi ; Cohn, Danny M ; Wedner, H James ; Kinaciyan, Tamar ; Rehman, Syed ; Ohsawa, Isao ; Craig, Timothy J ; Raasch, Jason P ; Busse, Paula J ; Aygören-Pürsün, Emel ; Kanarek, Henry J ; El-Shanawany, Tariq ; Manning, Michael E ; Lumry, William R ; Smith, Michael D ; Koleilat, Majed ; Li, H Henry ; Audhya, Paul K ; Fukunaga, Atsushi ; Iverson, Matthew ; Bernstein, Jonathan A ; Chuang, Ya-Hsiu ; Tachdjian, Raffi ; Soteres, Daniel F

Background:

Although long-term prophylaxis (LTP) reduces attack frequency in hereditary angioedema, patients may experience breakthrough attacks. Oral sebetralstat demonstrated favorable safety and efficacy compared with placebo in the randomized phase 3 KONFIDENT trial (NCT05259917), including in patients receiving LTP. The safety and effectiveness of sebetralstat in participants receiving LTP are being assessed in the KONFIDENT-S open-label extension study (NCT05505916).

Objective:

This interim analysis of the KONFIDENT-S study evaluated long-term safety and effectiveness of oral sebetralstat 600 mg for attacks of hereditary angioedema with C1-inhibitor deficiency in participants receiving LTP with lanadelumab, berotralstat, or C1 inhibitor.

Methods:

Efficacy end points included times to beginning of symptom relief, reduction in severity, and complete attack resolution.

Results:

As of September 14, 2024, 35 participants receiving LTP experienced a mean ± standard deviation of 1.7 ± 1.5 attacks per month and treated 382 attacks with sebetralstat (1.3 ± 1.1 sebetralstat-treated attacks per month). Median (interquartile range) time from attack recognition to sebetralstat administration was 6 (1-40) minutes; time to beginning of symptom relief was 1.3 (0.8 to 3.8) hours, time to reduction in severity was 4.2 (1.3 to >12) hours, and time to complete attack resolution was 14.8 (4.6 to >24) hours. Effectiveness was similar for participants receiving berotralstat, lanadelumab, or C1 inhibitor. No serious or severe treatment-related treatment-emergent adverse events were reported.

Conclusion:

Sebetralstat was well tolerated and enabled early on-demand treatment of attacks in patients with hereditary angioedema with C1-inhibitor deficiency receiving LTP. Treatment of breakthrough attacks with sebetralstat resulted in rapid symptom relief, reduction in attack severity, and complete attack resolution, regardless of LTP mechanism of action.

2026-08-01·ADVANCES IN THERAPY

Post Hoc Analysis of Recombinant C1 Inhibitor Clinical Data Using Contemporary Endpoints for Hereditary Angioedema

Article

作者: Gough, Adam ; Harper, Joseph R ; Harrington, Amanda ; Roskell, Neil ; Tachdjian, Raffi ; Habimana, Ketsia ; Narsipur, Nihal ; Jones, Douglas ; Li, H Henry ; Riedl, Marc A ; Kilvert, Hannah ; Relan, Anurag ; Aiello, Emily

INTRODUCTION:

Contemporary trials of medications to treat hereditary angioedema (HAE) attacks define efficacy endpoints using Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) scales; these differ from the visual analog scale (VAS) and treatment effect questionnaire (TEQ) used in legacy recombinant human C1 esterase inhibitor (rhC1-INH) studies. This post hoc analysis aimed to evaluate pooled rhC1-INH trial data, mapped to contemporary HAE clinical trial endpoints and designs.

METHODS:

Pooling data from three rhC1-INH trials for acute HAE attacks (NCT00225147, NCT01188564, NCT00262301), this analysis applied results from a bookmarking study to convert TEQ and VAS measurements to PGI-S and PGI-C scales. Kaplan-Meier estimates were calculated for time to complete resolution (TTCR; defined as "none" on PGI-S) and time to onset of symptom relief (TOSR; defined as "a little better" on PGI-C at ≥ 2 consecutive time points within 12 h). Log-rank tests were used to determine differences between treatment groups.

RESULTS:

Across trials, 48 and 60 patients received rhC1-INH 50 U/kg and placebo, respectively. The most common attack locations were peripheral (47.9% and 41.7%, respectively) and abdominal (35.4% and 35.0%, respectively). Baseline attack severity was either severe or very severe in all patients. Median [95% confidence interval (CI)] TOSR was 0.75 h (0.55-1.50) with rhC1-INH and 8.00 h (3.00-8.05) with placebo (P < 0.001). Median (95% CI) TTCR was 4.50 h (3.55-5.50) with rhC1-INH and 24.00 h (16.00- > 24.00) with placebo (P < 0.001).

CONCLUSION:

This post hoc analysis confirmed that rhC1-INH, compared with placebo, is associated with significantly shorter TOSR and TTCR of HAE attacks.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov: NCT00225147, NCT01188564, NCT00262301.

2026-07-01·ADVANCES IN THERAPY

Comparative Efficacy of Recombinant C1 Inhibitor Versus Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks: A Matching-Adjusted Indirect Treatment Comparison

Article

作者: Harrington, Amanda ; Roskell, Neil ; Jindal, Sakshi ; Jones, Douglas ; Narsipur, Nihal ; Li, H Henry ; Kilvert, Hannah ; Gough, Adam ; Habimana, Ketsia ; Relan, Anurag ; Anderson, John ; Aiello, Emily ; Smith, Andrew

INTRODUCTION:

Prompt and effective on-demand treatment is critical in hereditary angioedema (HAE). Although multiple on-demand therapies are available, including recombinant human C1 esterase inhibitor (rhC1-INH) and sebetralstat, no head-to-head efficacy trials exist.

METHODS:

A series of indirect treatment comparisons evaluated the relative efficacy of US Food and Drug Administration-approved doses of intravenous rhC1-INH (50 U/kg for patients weighing < 84 kg; 4200 U otherwise) vs oral sebetralstat (600 mg) for the on-demand treatment of HAE attacks. Patient-level data from rhC1-INH trials (C1 1310, C1 1205, and C1 1304 [placebo only]) were reweighted to match aggregate baseline characteristics (i.e., prophylaxis use, pooled attack location) from the sebetralstat KONFIDENT trial; matching variables were identified from a validated, clinician-informed study of treatment effect modifiers. In the primary analysis, time to complete resolution (TTCR) and redosing were compared using unanchored matching-adjusted indirect comparisons. TTCR subgroup analyses were performed for variables not matched for in the primary analysis due to population differences (i.e., attack severity, time to treatment). Scenario and sensitivity analyses were performed to support TTCR results; a scenario analysis was performed to support redosing results. Hazard ratios (HRs) and odds ratios (ORs), with 95% confidence intervals (CIs), were estimated using a weighted Cox proportional hazards model and a weighted logistic regression model, respectively.

RESULTS:

In the primary analysis, rhC1-INH was associated with a statistically significant 4.5-fold increased likelihood of achieving complete resolution (HR 4.52; 95% CI 2.84-7.18) and a significant 82% reduction in redosing (OR 0.18; 95% CI 0.06-0.53) vs sebetralstat. Similar results for TTCR were observed in subgroup analyses of patients with severe/very severe baseline attacks and patients receiving earlier treatment (within the median time to treatment). Scenario and sensitivity analyses confirmed the robustness of these findings.

CONCLUSIONS:

rhC1-INH provides significantly faster symptom resolution and lower redosing rates vs sebetralstat.

项与 Conestat alfa 相关的新闻（医药）

2026-07-30

·BioSpace

Pharming reports second quarter and first half 2026 financial results and revises year-end guidance; strong Joenja momentum and near-term clinical readouts to support broader therapeutic use

For investor audiences and media only Second quarter 2026 total revenues decreased by 3% to US$90.2 million, compared to the second quarter 2025 RUCONEST® revenue was US$72.3 million, a 10% decrease compared to the second quarter 2025 and a 24% increase compared to the first quarter 2026, with active patient base 93% of year-ago and strong new patient enrollments Joenja® revenue was US$17.9 million, a 40% increase compared to the second quarter 2025, reflecting continued strong U.S. and international growth, with first European launch in Germany after quarter-end Second quarter operating profit amounted to US$1.3 million compared to US$10.8 million in the second quarter 2025, impacted by manufacturing-related inventory impairments, lower revenue and France site closure Plans to report clinical data with leniolisib in significantly larger CVID patient populations in the fourth quarter 2026 Updates 2026 total revenue guidance to US$375 million - US$395 million, reflecting a US$30 million reduction, and improves operating expense guidance by US$15 million to US$315 million - US$320 million Pharming to host a conference call today at 13:30 CEST (7:30 am EDT) Leiden, the Netherlands, July 30, 2026: Pharming Group N.V. (Euronext Amsterdam: PHARM/Nasdaq: PHAR) presents its preliminary (unaudited) financial report for the second quarter and first half year ended June 30, 2026. Chief Executive Officer, Fabrice Chouraqui, commented: “While we have lowered our full-year revenue guidance, we are encouraged by the resilience of RUCONEST, a year after the launch of the first oral on-demand HAE treatment. The active patient base remained at 93% of year ago levels, and RUCONEST continues to be a cornerstone on-demand treatment for high-burden HAE patients. Supported by strong new patient enrollments in the second quarter, we expect RUCONEST revenues to stabilize and return to growth during the second half of 2026. Joenja (leniolisib) continued to build momentum in APDS, supported by expansion into additional geographies. Beyond APDS, we are encouraged by the potential for leniolisib in broader populations with primary immunodeficiencies, including CVID, where the PI3Kδ pathway is seen as a key driver of immune dysregulation, and we look forward to reporting data from two clinical trials in the fourth quarter of 2026. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); As we continue to implement a more disciplined operating model, reflected in our improved full-year operating expense guidance, Pharming is evolving into a more diversified rare disease company with a high-value pipeline that has the potential to materially increase our scale and strengthen our long-term growth profile.” Second quarter and first half 2026 highlights Commercialized assets RUCONEST marketed for the treatment of acute HAE attacks RUCONEST revenue in the second quarter of 2026 was US$72.3 million, a 10% decrease compared to the second quarter of 2025 and a 24% increase compared to the first quarter of 2026. Revenue for the first half of 2026 was US$130.7 million, a 12% decrease compared to the same period in 2025. RUCONEST revenue in the current quarter compared to the second quarter of 2025 was impacted by market dynamics in the U.S. (reducing revenue by 6%), inventory drawdowns at U.S. specialty pharmacy customers, and the completion of the planned withdrawal from non-U.S. markets. With its differentiated efficacy, reliability and rapid onset of action via IV administration, RUCONEST remains a trusted on-demand treatment option for high-burden patients experiencing more severe or frequent attacks who have failed other on-demand medications, despite increasing competition. The overwhelming majority of RUCONEST patients remain on therapy with the active patient base at 93% of year ago levels. Notably, we achieved a significant increase in new patient enrollments and continued to add new prescribers in the current quarter, indicating continued physician confidence and improvement in underlying performance. Joenja (leniolisib) marketed for the treatment of APDS Joenja revenue increased to US$17.9 million in the second quarter of 2026, a 40% increase compared to the second quarter of 2025. Revenue for the first half of 2026 was US$32.0 million, a 37% increase compared to the same period in 2025. Year-over-year revenue growth in the current quarter was driven by a strong increase in patients on paid therapy in the U.S., inventory normalization at U.S. specialty pharmacy customers following greater drawdowns in the first quarter, and increased demand in international markets. The U.S. market contributed 86% of second quarter revenues, while the EU and Rest of World contributed 14%. As of June 30, 2026, 132 patients were on paid therapy in the U.S., representing a 16% increase from the 114 patients at the end of the second quarter of 2025 and an increase of 5 patients during the quarter. APDS patient finding As of June 30, 2026, we have identified 1,042 diagnosed APDS patients of all ages globally, including 298 patients in the U.S. and 387 in core markets outside of the U.S. Of the identified patients in the U.S., 198 patients are 12 years of age or older and currently eligible for treatment with Joenja, while 60 are between 4 and 11 years of age. Joenja (leniolisib) development Leniolisib for APDS As of June 30, 2026, there are 188 APDS patients in either a leniolisib Expanded Access Program (compassionate use), an ongoing clinical study, or a paid access program. Pediatric label expansion On June 4, 2026, we announced that the U.S. Food and Drug Administration (FDA) had accepted our resubmitted supplemental New Drug Application (sNDA) seeking approval for Joenja as a treatment for children aged 4 to 11 years with APDS. Following the Complete Response Letter (CRL) received on January 30, 2026, and a subsequent Type A meeting with the FDA on March 26, 2026, the resubmission seeks approval of 40 mg and 50 mg twice-daily dosing for pediatric patients weighing 27 kg or more, who represent a meaningful proportion of the identified pediatric patient population. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 24, 2026. We plan to submit a separate sNDA in the coming days, seeking approval for lower doses in patients weighing 13 - 27 kg. Japan We expect to launch Joenja for the treatment of APDS in adult and pediatric patients aged 4 years and older in the third quarter of 2026. European Economic Area (EEA) On May 22, 2026, we announced that the European Commission (EC) had granted Marketing Authorization for Joenja as the first and only approved treatment of APDS in adult and pediatric patients 12 years of age and older. Joenja was commercially launched in Germany on July 1, 2026, marking the first European launch following EC approval, with additional launches anticipated pending completion of national reimbursement negotiations. Other countries On July 8, 2026, Joenja was approved by Health Canada for the treatment of APDS in adult and pediatric patients 12 years of age and older. On July 10, 2026, Joenja was approved by the South Korea Ministry of Food and Drug Safety for the treatment of APDS in adult and pediatric patients 12 years of age and older. Leniolisib for additional primary immunodeficiencies (PIDs) Two Phase II clinical trials are evaluating leniolisib for additional primary immunodeficiencies (PIDs) with immune dysregulation, including genetically identifiable PIDs linked to altered PI3Kδ signaling and common variable immunodeficiency or CVID, which represent substantially larger patient populations than APDS. Patient enrollment in both clinical trials is complete and we anticipate trial read-outs in the fourth quarter of 2026, consistent with prior guidance. The PI3Kδ pathway is seen as a key driver of immune dysregulation in many PIDs, and we currently anticipate conducting a single registrational Phase III trial in the broader CVID indication, incorporating patient populations from both studies. A presentation at the 2026 Annual Meeting of the Clinical Immunology Society (CIS), which took place May 6-9, included clinician expanded access experience with leniolisib to treat immune dysregulation in patients with CVID and CVID-like disorders. Clinician-reported outcomes demonstrated improvements, with no progression, in clinical manifestations of immune dysregulation as well as improvements in patients’ quality of life. Other events As we continue to improve operating efficiency in line with our strategy, we have decided to close our production-support site in Évry, France, with the closure expected to take effect in the fourth quarter of 2026. As a result, we recognized a one-time charge in the current quarter to reflect the estimated costs associated with the planned closure. Financial Summary Consolidated Statement of Income 2Q 2026 2Q 2025 1H 2026 1H 2025 Amounts in US$m except per share data Total Revenues 90.2 93.2 162.7 172.3 Cost of sales (14.5) (9.0) (21.2) (17.3) Gross profit 75.7 84.2 141.5 155.0 Other income 1.4 1.8 1.8 2.2 Research and development (32.3) (23.7) (57.8) (44.8) General and administrative (14.9) (20.5) (30.2) (43.0) Marketing and sales (28.6) (31.0) (58.9) (65.6) Other Operating Costs (75.8) (75.2) (146.9) (153.4) Operating profit (loss) 1.3 10.8 (3.6) 3.8 Finance result (net) and share of result in associates 1.8 (3.7) 1.9 (8.5) Profit (loss) before tax 3.0 7.1 (1.7) (4.7) Income tax credit (expense) (1.4) (2.5) (1.9) (5.6) Profit (loss) for the period 1.6 4.6 (3.6) (10.3) Earnings per share Basic, attributable to equity holders of the parent (US$) 0.003 0.007 (0.005) (0.015) Diluted, attributable to equity holders of the parent (US$) 0.002 0.006 (0.005) (0.015) Segment information - Revenues 2Q 2026 2Q 2025 1H 2026 1H 2025 Amounts in US$m Revenue - RUCONEST (US) 72.0 79.6 130.2 146.2 Revenue - RUCONEST (EU and RoW) 0.3 0.8 0.4 2.8 Total Revenues - RUCONEST 72.3 80.4 130.7 149.0 Revenue - Joenja (US) 15.4 11.8 26.9 21.3 Revenue - Joenja (EU and RoW) 2.5 1.0 5.1 2.0 Total Revenues - Joenja 17.9 12.8 32.0 23.3 Total Revenues - US 87.4 91.4 157.1 167.5 Total Revenues - EU and RoW 2.8 1.8 5.5 4.8 Total Revenues 90.2 93.2 162.7 172.3 Consolidated Balance Sheet June 30, 2026 December 31, 2025 Amounts in US$m Cash and cash equivalents, restricted cash and marketable securities 159.5 181.1 Current assets 280.7 299.5 Total assets 468.0 500.0 Current liabilities 93.2 115.8 Shareholders' equity 270.5 277.1 Figures may not add up due to rounding. Financial highlights Second quarter 2026 For the second quarter of 2026, total revenues decreased by US$3.0 million, or 3%, to US$90.2 million, compared to US$93.2 million in the second quarter of 2025. RUCONEST revenues amounted to US$72.3 million, a 10% decrease compared to the second quarter of 2025. The decrease in RUCONEST® revenues was primarily driven by a decrease in volume. Joenja revenues amounted to US$17.9 million in the second quarter of 2026, a 40% increase compared to the second quarter of 2025. This increase in Joenja revenues was primarily driven by an increase in volume. Gross profit decreased by US$8.5 million, or 10%, to US$75.7 million, compared to US$84.2 million in the second quarter of 2025, mainly due to manufacturing-related impairments of inventory (US$4.9 million) and the decrease in revenues. The operating profit amounted to US$1.3 million compared to US$10.8 million in the second quarter of 2025. Excluding US$4.9 million in one-time manufacturing-related impairments of inventory and US$1.7 million in expenses associated with the planned closure of the production-support site in Évry, France, adjusted operating profit 1 in the second quarter 2026 amounted to US$7.9 million. Excluding US$2.1 million of non-recurring Abliva acquisition-related expenses, adjusted operating profit in the second quarter 2025 amounted to US$12.9 million. The operating result was primarily impacted by manufacturing-related impairments of inventory and a decrease in revenues, while operating expenses remained similar to the second quarter of 2025. The finance result (net) and share of result in associates amounted to a gain of US$1.8 million compared to a loss of US$3.7 million in the second quarter of 2025. This improvement was mainly driven by favorable EUR/USD exchange rate movements, resulting in a foreign currency gain of US$2.9 million in 2026, compared to a loss of US$1.9 million in the second quarter of 2025. The Company had a net profit of US$1.6 million, compared to US$4.6 million in the second quarter of 2025. The effect of the aforementioned drivers was partially offset by a favorable change in the net finance result. Cash used in operations amounted to US$9.7 million, compared to US$11.7 million cash generated from operations in the second quarter of 2025. Cash and cash equivalents, restricted cash and marketable securities decreased from US$171.8 million at the end of first quarter of 2026 to US$159.5 million at the end of the second quarter of 2026, primarily driven by unfavorable working capital movements, mainly a decrease in trade and other payables and an increase in inventories, as well as income tax payments, partially offset by collections of trade and other receivables. 1 Adjusted Operating Profit is a non-IFRS measure used by management to assess underlying operating performance and provides additional insight into the Company's core operating profitability. It excludes certain non-core items. First half year 2026 Total revenues decreased 6% during the first half of 2026 to US$162.7 million, compared to US$172.3 million during the first half of 2025. For the first half of 2026, total RUCONEST revenues were 12% lower at US$130.7 million, compared to revenues of US$149.0 million for the first half of 2025. The decrease in RUCONEST revenues was primarily driven by a decrease in volume. Joenja revenues amounted to US$32.0 million in the first half of 2026, a 37% increase compared to the first half of 2025. This increase in Joenja revenues was primarily driven by an increase in volume. Gross profit decreased by US$13.5 million, or 9%, to US$141.5 million, compared to US$155.0 million in the first half of 2025, mainly due to the decrease in revenues and manufacturing-related impairments of inventory (US$4.9 million). Further details on revenue and gross profit segmentation is provided in Note 7. Segment informat ion in the Notes to the condensed consolidated interim financial statements of this press release. The operating loss amounted to US$3.6 million compared to an operating profit of US$3.8 million in the first half of 2025. Excluding US$4.9 million in one-time manufacturing-related impairments of inventory and US$1.7 million in expenses associated with the planned closure of the production-support site in Évry, France, adjusted operating profit in the first half 2026 amounted to US$3.0 million. Excluding US$9.9 million of non-recurring Abliva acquisition-related expenses, adjusted operating profit in the first half 2025 amounted to US$13.7 million. The deteriorated operating result was primarily driven by a decrease in revenues and manufacturing-related impairments of inventories in 2026. The finance result (net) and share result in associates amounted to a gain of US$1.9 million compared to a loss of US$8.5 million in the first half of 2025. This improvement was mainly driven by favorable EUR/USD exchange rate movements, resulting in a foreign currency gain of US$5.3 million in the first half year of 2026, compared to a loss of US$4.5 million in the first half year of 2025. The Company had a net loss of US$3.6 million, compared to a net loss of US$10.3 million in the first half of 2025. In addition to the aforementioned drivers, the net result was positively impacted by a lower tax expense of US$1.9 million compared to US$5.6 million in the first half of 2025. Cash used in operations amounted to US$7.7 million, compared to US$12.0 million of cash generated from operations in the first half of 2025. Cash and cash equivalents, restricted cash and marketable securities decreased by US$21.6 million to US$159.5 million from US$181.1 million at the end of 2025, primarily driven by negative working capital movements, increased income tax payments and US$12.3 million settlement of the lease liability following the early termination of the DSP facility lease at Pivot Park in Oss, the Netherlands. Outlook/Summary For 2026, the Company anticipates: Total revenues between US$375.0 million and US$395.0 million (0% to 5% growth), updated to reflect a US$30 million reduction compared with prior guidance. Total operating expenses between US$315.0 million and US$320.0 million (1% to 3% growth), including over US$40 million incremental R&D investment to advance the pipeline and US$9 million structural G&A cost reductions based on the plan announced in October 2025, reflecting an improvement of US$15 million from prior guidance. RUCONEST revenue stabilization and return to growth during second half of 2026, and significant and accelerating annual Joenja U.S. and ex-U.S. growth. Additional regulatory approvals and commercial launches for leniolisib for APDS patients 12 years of age or older and for pediatric label expansion in key global markets. Top-line data readouts for the two ongoing leniolisib Phase II clinical trials in PIDs with immune dysregulation, including CVID, to expand the asset’s addressable patient population. Completion of enrollment in the pivotal FALCON clinical study for napazimone (KL1333) in mitochondrial DNA-driven primary mitochondrial diseases. Enhancing capital efficiency to drive growth and build a leading global rare disease company. Continued focus on potential acquisitions and in-licensing of clinical stage opportunities in rare diseases. Financing, if required, would come via a combination of our strong balance sheet and access to capital markets. No further specific financial guidance for 2026 is provided. Trademarks Joenja® and RUCONEST® are registered trademarks owned by or licensed to Pharming Group N.V. or its affiliates. Additional information Presentation The conference call presentation is available on the Pharming.com website from 07:30 CEST today. Conference Call The conference call will begin at 13:30 CEST/07:30 EDT on Thursday, July 30. A transcript will be made available on the Pharming.com website in the days following the call. Please note, the Company will only take questions from dial-in attendees. Webcast Link: Conference call dial-in details: Additional information on how to register for the conference call/webcast can be found on the Pharming.com website. Financial Calendar 2026 3Q 2026 financial results November 5, 2026 For further public information, contact: Pharming Michael Levitan, VP Investor Relations and Capital Markets T: +1 (908) 705 1696 E: investor@pharming.com Saskia Mehring, Head of Corporate Communications T: +31 6 28 32 60 41 E: media.relations@pharming.com Media Relations Julia Deutsch (Lyra Strategic Advisory on behalf of Pharming) E: JDeutsch@lyraadvisory.com Netherlands: Leon Melens (LifeSpring Life Sciences Communication on behalf of Pharming) T: +31 6 53 81 64 27 About Pharming Group N.V. Pharming Group N.V. (Euronext Amsterdam: PHARM/Nasdaq: PHAR) is a global biopharmaceutical company dedicated to transforming the lives of patients with rare, debilitating, and life-threatening diseases. We develop and commercialize innovative medicines, including small molecules and biologics. Pharming is headquartered in Leiden, the Netherlands, with U.S. and European operations. For more information, visit and find us on LinkedIn . Auditor’s involvement The Condensed Consolidated Interim Financial Statements have not been audited by the Company’s statutory auditor. Responsibility Statement The Board of Directors of the Company (the “Board”) hereby declares that to the best of its knowledge, the condensed consolidated interim financial statements, which have been prepared in accordance with IAS 34 (interim financial reporting), give a true and fair view of the assets, liabilities, financial position and profit or loss of the Company, and this interim Board report includes a fair review of the information required pursuant to section 5:25d(8) and (9) of the Dutch Financial Supervision Act (Wet op het financieel toezicht). Leiden, July 30, 2026 Fabrice Chouraqui, Chief Executive Officer and Executive Director Richard Peters, Non-Executive Director and Chairman of the Board of Directors Mark Pykett, Non-Executive Director Barbara Yanni, Non-Executive Director Leonard Kruimer, Non-Executive Director Jabine van der Meijs, Non-Executive Director Elaine Sullivan, Non-Executive Director Forward-looking Statements This press release may contain forward-looking statements. Forward-looking statements are statements of future expectations that are based on management’s current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in these statements. These forward-looking statements are identified by their use of terms and phrases such as “aim”, “ambition”, ‘‘anticipate’’, ‘‘believe’’, ‘‘could’’, ‘‘estimate’’, ‘‘expect’’, ‘‘goals’’, ‘‘intend’’, ‘‘may’’, “milestones”, ‘‘objectives’’, ‘‘outlook’’, ‘‘plan’’, ‘‘probably’’, ‘‘project’’, ‘‘risks’’, “schedule”, ‘‘seek’’, ‘‘should’’, ‘‘target’’, ‘‘will’’ and similar terms and phrases. Examples of forward-looking statements may include statements with respect to timing and progress of Pharming's preclinical studies and clinical trials of its product candidates, Pharming's clinical and commercial prospects, and Pharming's expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharming's clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory, commercial, competitive and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's 2025 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2025, filed with the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forward-looking statements may not occur, and Pharming's actual results could differ materially and adversely from those anticipated or implied thereby. All forward-looking statements contained in this press release are expressly qualified in their entirety by the cautionary statements contained or referred to in this section. Readers should not place undue reliance on forward-looking statements. Any forward-looking statements speak only as of the date of this press release and are based on information available to Pharming as of the date of this release. Pharming does not undertake any obligation to publicly update or revise any forward-looking statement as a result of new information, future events or other information. Inside Information This press release relates to the disclosure of information that qualifies, or may have qualified, as inside information within the meaning of Article 7(1) of the EU Market Abuse Regulation. Pharming Group N.V. Condensed Consolidated Interim Financial Statements in US Dollars (unaudited) For the period ended June 30, 2026 Condensed consolidated interim statement of income Condensed consolidated interim statement of comprehensive income Condensed consolidated interim balance sheet Condensed consolidated interim statement of changes in equity Condensed consolidated interim statement of cash flow CONDENSED CONSOLIDATED INTERIM STATEMENT OF INCOME (UNAUDITED) For the period ended June 30 Amounts in US$ ‘000 notes 1H 2026 1H 2025 Revenues 7 162,660 172,315 Costs of sales 9 (21,189) (17,295) Gross profit 7 141,471 155,020 Other income 8 1,801 2,232 Research and development (57,819) (44,837) General and administrative (30,165) (42,991) Marketing and sales (58,886) (65,619) Other Operating Costs 9 (146,870) (153,447) Operating profit (loss) (3,598) 3,805 Other finance income 10 7,119 1,263 Other finance expenses 10 (5,403) (9,785) Finance result, net 1,716 (8,522) Share of net profits (loss) in associates using the equity method 12 168 8 Profit (loss) before tax (1,714) (4,709) Income tax credit (expense) 11 (1,861) (5,629) Profit (loss) for the period (3,575) (10,338) Attributable to: Equity holders of the parent (3,575) (10,025) Non-controlling interests — (313) Earnings per share Basic earnings per share (US$) 18 (0.005) (0.015) Diluted earnings per share (US$) 18 (0.005) (0.015) CONDENSED CONSOLIDATED INTERIM STATEMENT OF COMPREHENSIVE INCOME (UNAUDITED) For the period ended June 30 Amounts in US$ ‘000 1H 2026 1H 2025 Profit (loss) for the period (3,575) (10,338) Currency translation differences (8,433) 26,148 Items that may be subsequently reclassified to profit or loss (8,433) 26,148 Other comprehensive income (loss), net of tax (8,433) 26,148 Total comprehensive income (loss) for the period (12,008) 15,810 Attributable to: Equity holders of the parent (12,008) 16,123 Non-controlling interests — (313) CONDENSED CONSOLIDATED INTERIM BALANCE SHEET (UNAUDITED) Amounts in US$ ‘000 notes June 30, 2026 December 31, 2025 Non-current assets Intangible assets 128,082 135,538 Property, plant and equipment 6,425 7,233 Right-of-use assets 14,058 16,738 Long-term prepayments 92 94 Deferred tax assets 13 28,838 31,017 Investment accounted for using the equity method 12 2,055 1,944 Investment in debt instruments designated as at FVTPL 12 6,520 6,703 Restricted cash 1,225 1,227 Total non-current assets 187,295 200,495 Current assets Inventories 14 65,428 64,902 Trade and other receivables 56,980 54,704 Restricted cash — 761 Marketable securities 15 — 33,796 Cash and cash equivalents 15 158,281 145,305 Total current assets 280,689 299,469 Total assets 467,984 499,963 Equity Share capital 8,081 8,009 Share premium 520,312 513,257 Other reserves 20,342 28,819 Accumulated deficit (278,245) (272,983) Total equity 16 270,490 277,102 Non-current liabilities Convertible bonds 17 92,401 92,719 Lease liabilities 11,848 14,351 Total non-current liabilities 104,249 107,070 Current liabilities Convertible bonds 17 5,469 5,336 Provisions 1,878 1,187 Trade and other payables 82,321 105,899 Lease liabilities 3,577 3,369 Total current liabilities 93,245 115,791 Total equity and liabilities 467,984 499,963 CONDENSED CONSOLIDATED INTERIM STATEMENT OF CHANGES IN EQUITY (UNAUDITED) For the period ended June 30 Attributable to equity holders of the parent Amounts in US$ ‘000 notes Share capital Share premium Other reserves Accumulated deficit Subtotal Non-controlling interests Total equity Balance at January 1, 2025 7,769 488,990 (209) (275,489) 221,061 — 221,061 Profit (loss) for the period — — — (10,025) (10,025) (313) (10,338) Other comprehensive income (loss) for the period — — 26,148 — 26,148 — 26,148 Total comprehensive income (loss) for the period — — 26,148 (10,025) 16,123 (313) 15,810 Movement in reserves 16 — — (31) 31 — — — Income tax benefit from excess tax deductions related to share-based payments — — — (209) (209) — (209) Share-based compensation — — — 6,052 6,052 — 6,052 Options exercised / LTIP shares issued 52 2,863 — (4,273) (1,358) — (1,358) Acquisition of a subsidiary — — — — — 6,133 6,133 Acquisition of non-controlling interests — — — (2,118) (2,118) (5,820) (7,938) Total transactions with owners, recognized directly in equity 52 2,863 (31) (517) 2,367 313 2,680 Balance at June 30, 2025 7,821 491,853 25,908 (286,031) 239,551 — 239,551 Balance at January 1, 2026 8,009 513,257 28,819 (272,983) 277,102 — 277,102 Profit (loss) for the period — — — (3,575) (3,575) — (3,575) Other comprehensive income (loss) for the period — — (8,433) — (8,433) — (8,433) Total comprehensive income (loss) for the period — — (8,433) (3,575) (12,008) — (12,008) Movement in reserves 16 — — (44) 34 (10) — (10) Income tax expense from excess tax deductions related to share-based payments — — — 248 248 — 248 Share-based compensation — — — 6,575 6,575 — 6,575 Options exercised / LTIP shares issued 71 7,056 — (8,545) (1,418) — (1,418) Total transactions with owners, recognized directly in equity 71 7,056 (44) (1,688) 5,395 — 5,395 Balance at June 30, 2026 8,081 520,312 20,342 (278,245) 270,490 — 270,490 2 Comparative presentation updated for consistency. CONDENSED CONSOLIDATED INTERIM STATEMENT OF CASH FLOWS (UNAUDITED) For the period ended June 30 Amounts in $’000 1H 2026 1H 2025 Profit (loss) before tax (1,714) (4,709) Adjustments to reconcile net profit (loss) to net cash used in operating activities: Depreciation, amortization, impairment of non-current assets 6,154 5,284 Equity settled share based payments 6,575 6,052 Loss (gain) on disposal of leases 38 (10) Impairments of inventories² 5,990 3,742 Other finance income (7,119) (1,263) Other finance expenses 5,371 9,650 Share of net losses (gains) in associates using the equity method (168) (8) Operating cash flows before changes in working capital 15,127 18,738 Changes in working capital: Inventories² (7,256) (4,051) Trade and other receivables 1,320 2,359 Payables and other current liabilities (13,159) 1,031 Provisions 691 — Restricted cash 709 (3,052) Total changes in working capital (17,695) (3,713) Interest received 1,266 1,273 Income taxes received (paid) (6,404) (4,323) Net cash flows generated from (used in) operating activities (7,706) 11,975 Capital expenditure for property, plant and equipment (321) (410) Investment intangible assets — (6) Investment in associates using the equity method — (429) Purchases of marketable securities (102,646) — Proceeds from sale of marketable securities 18,124 84,967 Acquisition of a subsidiary, net of cash acquired — (57,476) Net cash flows generated from (used in) investing activities (84,843) 26,646 Payment of lease liabilities (13,894) (1,781) Interests on lease liabilities (242) (562) Interests on convertible bonds (2,630) (2,450) Exercise of share-based compensation awards 5,098 1,287 Acquisition of non-controlling interests — (5,970) Net cash flows generated from (used in) financing activities (11,668) (9,476) Increase (decrease) of cash (104,217) 29,145 Exchange rate effects (603) 8,002 Effect of reclassification of money market funds to cash equivalents (see note 15) 117,796 — Cash and cash equivalents at January 1 145,305 54,944 Total cash and cash equivalents at June 30 158,281 92,091 Notes to the condensed consolidated interim financial statements For the period ended June 30, 2026 1. Company information Pharming Group N.V. is a limited liability public company which is listed on Euronext Amsterdam (PHARM) and on the NASDAQ (PHAR), with its headquarters and registered office located at: Darwinweg 24 2333 CR Leiden The Netherlands Pharming Group N.V. is a global biotechnology company that develops and commercializes innovative therapies for rare and ultra-rare diseases with significant unmet need. We focus on immunological and genetic conditions where our scientific and commercial expertise can help advance care over the long term. 2. Statement of compliance The consolidated interim financial statements for the six-month period ended June 30, 2026, have been prepared in accordance with International Accounting Standard IAS 34, Interim financial reporting. The condensed consolidated interim financial statements should be read in conjunction with the annual financial statements for the year ended December 31, 2025. They do not include all of the information required for a complete set of financial statements in accordance with IFRS Accounting Standards. However, selected explanatory notes are included to explain events and transactions that are significant to an understanding of the changes in the Group’s financial position and performance since the last annual financial statements. These condensed consolidated interim financial statements were authorized for issue by the Board of Directors on July 29, 2026. The published figures in these condensed consolidated interim financial statements are unaudited. 3. Accounting policies Accounting policies are consistent with those of the financial statements for the year ended December 31, 2025. The following exchange rates have been applied: Applied exchange rates June 30, 2026 Average 1H 2026 December 31, 2025 Average 1H 2025 EUR/USD 1.1394 1.1687 1.1713 1.0889 AUD/USD 0.6887 0.7017 0.6699 0.6322 GBP/USD 1.3221 1.3458 1.3455 1.2992 SEK/USD 0.1027 0.1084 0.1083 0.0981 4. Estimates and judgements The preparation of interim financial statements in conformity with IAS 34 and Book 2 Title 9 of the Dutch Civil Code requires the use of certain critical accounting estimates. It also requires management to exercise its judgement in the process of applying the Company’s accounting policies. In preparing these condensed consolidated interim financial statements, the significant judgements made by management in applying the Company’s accounting policies were the same as those applied to the consolidated financial statements for the year ended December 31, 2025. 5. Going concern In preparing and finishing the interim financial statements the Board of Directors of Pharming have assessed the Company’s ability to fund its operations for a period of at least twelve months after the date the interim financial statements are issued. Based upon the assessment on a going concern basis, the Company has concluded that funding of its operations for a period of twelve months, after the date the interim financial statements are issued, is realistic and achievable. Overall, based on the outcome of this assessment, the interim financial statements have been prepared on a going concern basis. 6. Seasonality of operations Seasonality has no material impact on Company’s interim financial statements. 7. Segment information Operating segments are components of the Company that engage in business activities from which it may incur expenses, for which discrete financial information is available and whose operating results are evaluated regularly by the Company’s Chief Operating Decision Maker (“CODM”) to make decisions about resources to be allocated to the segment and assess its performance. The Executive Members of the Board of Directors are considered the CODM. CODM reviews the Company’s results under four operating segments based on a combination of the products that the Company has launched - RUCONEST and Joenja, and the main geographies where sales are consummated - focused on the US and reporting, in aggregate, EU and Rest of the World (“RoW”). The four operating segments correspond to each of its four reportable segments for financial reporting purposes. The CODM reviews revenues and gross profit to assess the performance of their operating segments, which are the sole performance measures on segment level which are provided regularly to the CODM. No other information, such as operating expenses, assets or other performance indicators on segment level are provided regularly to the CODM. Total revenues and gross profit per each operating and reportable segment for the period ended June 30 are: Amounts in US$ ‘000 1H 2026 1H 2025 RUCONEST Joenja Total RUCONEST Joenja Total Revenues: US 130,225 26,944 157,169 146,244 21,272 167,516 EU and RoW 439 5,052 5,491 2,759 2,040 4,799 Total revenues 130,664 31,996 162,660 149,003 23,312 172,315 Gross profit: US 112,971 23,472 136,443 134,211 18,448 152,659 EU and RoW 176 4,852 5,028 340 2,021 2,361 Total gross profit 113,147 28,324 141,471 134,551 20,469 155,020 There are no intersegment sales. 8. Other income Other income decreased by US$0.4 million in the first half of 2026 to US$1.8 million as compared to US$2.2 million the first half of 2025. 9. Expenses by nature Costs of sales Amounts in US$ ‘000 1H 2026 1H 2025 Cost of inventories recognized as expenses (12,681) (13,199) Royalty fees (3,361) (2,421) Inventory impairments (5,147) (1,675) Total (21,189) (17,295) Costs of inventories recognized as expenses in the first half year of 2026 were US$12.7 million versus US$13.2 million for the first half of 2025 and relates to actual product sales of RUCONEST and Joenja. Pharming expensed royalty fees to Novartis on Joenja sales, amounting to US$3.4 million in the first half of 2026 (first half of 2025: US$2.4 million). Inventory impairments amounted to US$5.1 million (1H 2025: US$1.7 million) and stems from the valuation of the inventories against lower net realizable value and mainly relates to material no longer expected to be used for commercial sales. Other operating costs Other operating costs decreased to US$146.9 million in the first half of 2026 compared to US$153.4 million in the first half year of 2025. Employee benefits are charged to research and development costs, general and administrative costs, or marketing and sales costs based on the nature of the services provided. Employee benefits of production related employees have been included in the value of inventories. Depreciation and amortization charges amounted to US$6.0 million in the first half of 2026 compared to US$5.3 million the first half year of 2025, and related to the following: Amounts in US$ ‘000 1H 2026 1H 2025 Property, plant and equipment (616) (650) Right-of-use assets (1,494) (1,475) Intangible assets (3,860) (3,159) Total (5,970) (5,284) 10. Finance income (expenses) Amounts in US$ ‘000 1H 2026 1H 2025 Foreign currency results 5,303 — Interest income 1,816 1,263 Other finance income 7,119 1,263 Foreign currency results — (4,549) Fees and expenses on repayment and issuance convertible bonds — — Amortization and interest on convertible bonds (5,179) (4,586) Interest leases (192) (516) Other finance expenses (32) (136) Other finance expenses (5,403) (9,787) Total other finance income and expenses 1,716 (8,524) Foreign currency results primarily reflect movements in the EUR/USD exchange rate. The strengthening of the U.S. dollar against the euro during the first half of 2026 (compared with a weakening during the first half of 2025) generated foreign exchange gains. These gains were mainly attributable to the revaluation of the U.S. dollar-denominated cash and marketable securities balances held by euro functional currency entities and euro-denominated monetary assets and liabilities held by the U.S. dollar functional currency entity. Interest income increased compared with the first half of 2025 due to a higher average balance of cash and marketable securities following the completion of the Abliva acquisition in the first half of 2025, as well as higher effective yields earned on cash and cash equivalents. 11. Income tax (expenses) Income tax expenses are recognized in each interim period based on the best estimate of the weighted average annual effective income tax rate expected for the full financial year. 12. Investments Investments accounted for using the equity method The asset relates to an investment in the ordinary shares of BioConnection Investments B.V. (“BioConnection”). In the Board of Directors’ judgement, the investment in BioConnection constitutes an investment in an associated company and is therefore not consolidated. Pharming has significant influence but does not have control of BioConnection and is embargoed by a shareholder’s agreement between the shareholders of BioConnection from influencing any activity between the two parties which is in any significant way different from the relationship which existed between the two prior to the investment. The carrying amount of this investment has changed as follows: Amounts in US$ ‘000 Period to June 30, 2026 Period to December 31, 2025 Balance at January 1 1,944 466 Share in net profit (loss) for the period 168 623 Equity contribution — 739 Currency translation (57) 116 Balance at end of period 2,055 1,944 Investment in debt instruments designated as at FVTPL The asset relates to the preference share in BioConnection Investments B.V. The Board of Directors made an assessment on the accounting treatment of the preference share obtained. The Board concluded that the asset should be recognized as a financial asset (debt instrument) measured at initial recognition at fair value, subsequently measured at fair value through profit and loss. The fair value is calculated on a yearly basis using the forward-looking Black-Scholes-Merton (“BSM”) financial instrument pricing framework. No events or matters are known as of the date of this report which would lead to a significant impact in the fair value of the asset, compared to December 31, 2025. The carrying amount of this investment has changed as follows: Amounts in US$ ‘000 Period to June 30, 2026 Period to December 31, 2025 Balance at January 1 6,703 3,767 Fair value changes — 2,345 Currency translation (183) 591 Balance at end of period 6,520 6,703 13. Deferred tax assets The deferred tax assets decreased mainly due to foreign exchange effects and changes in temporary differences. 14. Inventories Inventories include batches of Joenja and RUCONEST and related work in progress. Amounts in US$ ‘000 June 30, 2026 December 31, 2025 Finished goods 16,406 18,214 Work in progress 49,022 46,688 Balance at end of period 65,428 64,902 Changes in the adjustment to net realizable value: Amounts in US$ ‘000 Period to June 30, 2026 Period to December 31, 2025 Balance at January 1 (13,060) (8,663) Addition to impairment (6,195) (6,193) Release of impairment 206 538 Usage of impairment 2,011 2,522 Currency translation 455 (1,264) Balance at end of period (16,583) (13,060) The inventory valuation at June 30, 2026, of US$65.4 million (December 31, 2025: US$64.9 million) is stated net of an impairment of US$16.6 million (December 31, 2025: US$13.1 million). The impairment relates to the write down of inventories to their net realizable value. Inventories are available for use in commercial, preclinical and clinical activities. Estimates have been made with respect to the ultimate use or sale of product, taking into account current and expected sales as well as preclinical and clinical programs. These estimates are reflected in the additions to the impairment. The costs of materials used in research and development activities are presented under the research and development costs. The main portion of inventories at June 30, 2026, have expiration dates starting beyond 2026 and are all expected to be sold and/or used before expiration. Cash, cash equivalents and marketable securities Amounts in US$ ‘000 June 30, 2026 December 31, 2025 Investments in money market funds — 33,796 Marketable securities — 33,796 Cash held at banks 60,007 145,305 Investments in money market funds 98,274 — Cash and cash equivalents 158,281 145,305 Total liquidity 158,281 179,101 Since April 1, 2026, the marketable securities are considered to be cash equivalents as they are managed from that date as part of the Group’s total liquidity position and are held to meet potential short-term cash commitments rather than for investment purposes. The money market funds consist of LVNAV money market funds regulated under the EU Money Market Fund Regulation, which imposes liquidity, maturity, diversification and credit quality requirements broadly comparable to those applicable to SEC Rule 2a‑7 money market funds. The carrying value includes accrued interest of US$0.3 million as of June 30, 2026 (December 31, 2025: US$0.1 million). Cash is free at disposal of the Company. 16. Equity The Company’s authorized share capital amounts to €10.56 million (US$12.0 million) and is divided into 1,056,000,000 ordinary shares with a nominal value of €0.01 each. All 707,781,240 shares outstanding at June 30, 2026, have been fully paid-up. Other reserves include those reserves related to currency translation, share-based compensation expenses and other equity-settled transactions. Please refer to the Condensed consolidated interim statement of changes in Equity. The other reserves are made up as shown in the below table. Amounts in US$ ‘000 Legal reserve Currency translation reserve (CTA) Legal Reserve Capitalized development cost Reserve Convertible bond Total Balance at January 1, 2025 (12,510) 76 12,225 (209) Movement in the period 26,148 (31) — 26,117 Balance at June 30, 2025 13,638 45 12,225 25,908 Balance at January 1, 2026 14,941 44 13,835 28,819 Movement in the period (8,057) (44) (377) (8,477) Balance at June 30, 2026 6,884 — 13,458 20,342 17. Convertible bonds In April 2024, the Company issued €100.0 million (US$113.9 million, based on the EUR/USD exchange rate as of June 30, 2026) aggregate principal amount of 4.50% convertible bonds due 2029. The movements of the convertible bonds were as follows: Amounts in US$ ‘000 Period to June 30, 2026 Period to December 31, 2025 Balance at January 1 98,055 82,399 Interest paid (cash flow) (2,630) (5,067) Amortization 4,230 8,752 Accrued interest 949 933 Currency translation (2,734) 11,038 Carrying value at end of period 97,870 98,055 18. Earnings per share and diluted shares Basic earnings per share is calculated based on the weighted average number of ordinary shares outstanding during the period. Diluted earnings per share in the case of a profit is computed based on the weighted average number of ordinary shares outstanding including the dilutive effect of shares to be issued in the future under certain arrangements such as option plans. However, as the net result represents a loss, the diluted earnings per share are equal to the basic earnings per share. For 1H 2026 and 1H 2025, the basic and diluted earnings per share are: 1H 2026 1H 2025 Net profit (loss) attributable to equity owners of the parent (in US $ '000) (3,575) (10,025) Weighted average shares outstanding (in '000) 705,383 677,743 Basic profit (loss) per share (in US$) (0.005) (0.015) Weighted average fully-diluted shares outstanding (in '000) 749,519 744,282 Fully-diluted profit per share (in US$) (0.005) (0.015) Diluted shares The composition of the number of shares and share rights outstanding as well as authorized share capital as per June 30, 2026 is provided in the table below: Amounts in '000 December 31, 2025 Shares issued Other June 30, 2026 Issued shares 701,680,440 6,100,800 — 707,781,240 RSU 19,853,668 (726,337) (2,185,735) 16,941,596 Options 8,479,908 (2,758,750) (60,000) 5,661,158 Convertible bonds 81,492,951 — — 81,492,951 LTIP 19,636,796 (3,287,161) 3,818,129 20,167,764 Fully-diluted shares 831,143,763 (671,448) 1,572,394 832,044,709 Available for issue 224,856,237 671,448 (1,572,394) 223,955,291 Authorized share capital 1,056,000,000 — — 1,056,000,000 19. Financial risk management and fair value Financial risk management Pharming is exposed to several financial risks: market risks (being currency risk and interest rate risk), credit risks and liquidity risks. The Board of Directors and the Executive Committee are responsible for the management of currency, interest, credit and liquidity risks and as such ultimately responsible for decisions taken in this field. The Group’s exposure to financial risks has not materially changed during the period. Fair value The following table provides information on the fair value of financial instruments not measured at fair value as at the reporting date: June 30, 2026 December 31, 2025 Carrying value Fair value Carrying value Fair value Liabilities: Convertible Bond (incl. equity component) 111,328 145,807 111,890 157,481 For financial instruments not included in the table above, the carrying amount is a reasonable approximation of fair value. The following table presents information on the fair value measurement hierarchy of financial instruments measured at fair value: June 30, 2026 December 31, 2025 Level 1 Level 3 Total Level 1 Level 3 Total Items measured at fair value: Money market funds 98,274 — 98,274 33,796 — 33,796 Investments in debt instruments designated as at FVTPL — 6,520 6,520 — 6,703 6,703 Items for which fair value is disclosed: Convertible Bond (incl. equity component) 145,807 — 145,807 157,481 — 157,481 Further information on the investments in debt instruments designated as at FVTPL is included in note 12. During the six-month period ended June 30, 2026, there have been no changes related to the fair value hierarchy. Comparative information was updated for consistency. 20. Related party transactions There are no material changes in the nature, scope, and scale in this reporting period compared to last year. More information is included in note 24 to the consolidated financial statements as at and for the year ended December 31, 2025. 21. Events since the end of the reporting period There were no significant events since the end of the reporting period. Attachment Pharming Group reports 2Q_1H26 results_EN_30JULY2026

2026-07-29

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Pharming公布2026年第二季度及上半年财务业绩并修订全年指引；Joenja势头强劲，近期临床数据读出将支持更广泛的治疗应用Pharming reports second quarter and first half 2026 financial results and revises year-end guidance; strong Joenja momentum and near-term clinical readouts to support broader therapeutic use

For investor audiences and media only 仅限投资者和媒体Second quarter 2026 total revenues decreased by 3% to US$90.2 million, compared to the second quarter 2025 2026年第二季度总营收为9,020万美元，较2025年第二季度下降3%RUCONEST® revenue was US$72.3 million, a 10% decrease compared to the second quarter 2025 and a 24% increase compared to the first quarter 2026, with active patient base 93% of year-ago and strong new patient enrollments RUCONEST® 的收入为7,230万美元，较2025年第二季度下降10%，较2026年第一季度增长24%；活跃患者基数为去年同期的93%，新患者入组情况强劲。Joenja® revenue was US$17.9 million, a 40% increase compared to the second quarter 2025, reflecting continued strong U.S. and international growth, with first European launch in Germany after quarter-end Joenja® 的收入为1,790万美元，较2025年第二季度增长40%，反映出美国及国际市场持续强劲的增长势头，且在季度结束后于德国完成了欧洲市场的首次上市。Second quarter operating profit amounted to US$1.3 million compared to US$10.8 million in the second quarter 2025, impacted by manufacturing-related inventory impairments, lower revenue and France site closure 第二季度营业利润为130万美元，而2025年第二季度为1,080万美元，受到与制造相关的存货减值、收入下降以及法国工厂关闭的影响。Plans to report clinical data with leniolisib in significantly larger CVID patient populations in the fourth quarter 2026 计划在2026年第四季度报告在更大规模的常见变异型免疫缺陷病（CVID）患者人群中开展的leniolisib临床试验数据Updates 2026 total revenue guidance to US$375 million - US$395 million, reflecting a US$30 million reduction, and improves operating expense guidance by US$15 million to US$315 million - US$320 million 将2026年全年营收指引下调3,000万美元，至3.75亿美元–3.95亿美元；同时将运营费用指引优化1,500万美元，至3.15亿美元–3.20亿美元Pharming to host a conference call today at 13:30 CEST (7:30 am EDT) Pharming 将于今天欧洲中部夏令时间 13:30（美国东部夏令时间上午 7:30）举行电话会议Leiden, the Netherlands, July 30, 2026: 荷兰莱顿，2026年7月30日：Pharming Group N.V. (Euronext Amsterdam: PHARM/Nasdaq: PHAR) presents its preliminary (unaudited) financial report for the second quarter and first half year ended June 30, 2026. Pharming Group N.V.（泛欧交易所阿姆斯特丹：PHARM/纳斯达克：PHAR）公布截至2026年6月30日的第二季度及上半年初步（未经审计）财务报告。Chief Executive Officer, Fabrice Chouraqui, commented: 首席执行官法布里斯·舒拉基评论道：“While we have lowered our full-year revenue guidance, we are encouraged by the resilience of RUCONEST, a year after the launch of the first oral on-demand HAE treatment. The active patient base remained at 93% of year ago levels, and RUCONEST continues to be a cornerstone on-demand treatment for high-burden HAE patients. “尽管我们下调了全年收入指引，但在首款口服按需HAE治疗药物推出一年后，RUCONEST展现出的韧性令我们备受鼓舞。活跃患者基数保持在去年同期水平的93%，RUCONEST继续作为高负担HAE患者按需治疗的基石。”Supported by strong new patient enrollments in the second quarter, we expect RUCONEST revenues to stabilize and return to growth during the second half of 2026.. 在第二季度强劲的新患者入组支持下，我们预计RUCONEST的收入将在2026年下半年企稳并恢复增长。Joenja (leniolisib) continued to build momentum in APDS, supported by expansion into additional geographies. Beyond APDS, we are encouraged by the potential for leniolisib in broader populations with primary immunodeficiencies, including CVID, where the PI3Kδ pathway is seen as a key driver of immune dysregulation, and we look forward to reporting data from two clinical trials in the fourth quarter of 2026.. Joenja（leniolisib）在APDS治疗领域持续势头强劲，这得益于其市场覆盖范围扩展至更多地区。除APDS外，我们对leniolisib在更广泛的原发性免疫缺陷患者群体（包括CVID）中的应用潜力感到鼓舞；在这些疾病中，PI3Kδ通路被视为免疫失调的关键驱动因素。我们期待在2026年第四季度公布两项临床试验的数据。As we continue to implement a more disciplined operating model, reflected in our improved full-year operating expense guidance, Pharming is evolving into a more diversified rare disease company with a high-value pipeline that has the potential to materially increase our scale and strengthen our long-term growth profile.”. “随着我们持续推进更加规范的运营模式（这体现在我们对全年运营费用指引的改善上），Pharming 正在转型为一家更具多元化的罕见病公司，拥有高价值的产品管线，有望显著提升我们的规模并增强长期增长前景。”Second quarter and first half 2026 highlights 2026年第二季度及上半年亮点Commercialized assets 商业化资产RUCONEST marketed for the treatment of acute HAE attacks RUCONEST 获批用于治疗急性遗传性血管性水肿发作RUCONEST revenue in the second quarter of 2026 was US$72.3 million, a 10% decrease compared to the second quarter of 2025 and a 24% increase compared to the first quarter of 2026. Revenue for the first half of 2026 was US$130.7 million, a 12% decrease compared to the same period in 2025. 2026年第二季度，RUCONEST的收入为7,230万美元，较2025年第二季度下降10%，较2026年第一季度增长24%。2026年上半年的收入为1.307亿美元，较2025年同期下降12%。RUCONEST revenue in the current quarter compared to the second quarter of 2025 was impacted by market dynamics in the U.S. (reducing revenue by 6%), inventory drawdowns at U.S. specialty pharmacy customers, and the completion of the planned withdrawal from non-U.S. markets. 与2025年第二季度相比，本季度RUCONEST的收入受到美国市场动态（导致收入减少6%）、美国专业药房客户库存下降以及按计划完成退出非美国市场的影响。With its differentiated efficacy, reliability and rapid onset of action via IV administration, RUCONEST remains a trusted on-demand treatment option for high-burden patients experiencing more severe or frequent attacks who have failed other on-demand medications, despite increasing competition. The overwhelming majority of RUCONEST patients remain on therapy with the active patient base at 93% of year ago levels. 凭借差异化的疗效、可靠性以及静脉给药带来的快速起效特点，尽管面临日益激烈的竞争，RUCONEST 仍然是那些遭受更严重或更频繁发作、且其他按需治疗药物失败的高负担患者所信赖的按需治疗选择。绝大多数 RUCONEST 患者仍在持续接受治疗，活跃患者数量维持在一年前水平的 93%。Notably, we achieved a significant increase in new patient enrollments and continued to add new prescribers in the current quarter, indicating continued physician confidence and improvement in underlying performance.. 值得注意的是，我们在本季度实现了新患者入组的显著增长，并持续新增处方医生，这表明医生对我们的信心持续增强，基础业绩也在不断改善。Joenja (leniolisib) marketed for the treatment of APDS Joenja（leniolisib）已上市，用于治疗APDSJoenja revenue increased to US$17.9 million in the second quarter of 2026, a 40% increase compared to the second quarter of 2025. Revenue for the first half of 2026 was US$32.0 million, a 37% increase compared to the same period in 2025. Joenja在2026年第二季度的营收增至1,790万美元，较2025年第二季度增长40%。2026年上半年营收为3,200万美元，较2025年同期增长37%。Year-over-year revenue growth in the current quarter was driven by a strong increase in patients on paid therapy in the U.S., inventory normalization at U.S. specialty pharmacy customers following greater drawdowns in the first quarter, and increased demand in international markets. 本季度营收同比增长主要得益于美国付费治疗患者数量的强劲增长、美国专科药房客户在第一季度大幅去库存后库存回归正常水平，以及国际市场需求的增加。The U.S. market contributed 86% of second quarter revenues, while the EU and Rest of World contributed 14%. 美国市场贡献了第二季度收入的86%，而欧盟和世界其他地区贡献了14%。As of June 30, 2026, 132 patients were on paid therapy in the U.S., representing a 16% increase from the 114 patients at the end of the second quarter of 2025 and an increase of 5 patients during the quarter. 截至2026年6月30日，美国有132名患者正在接受付费治疗，较2025年第二季度末的114名患者增长16%，本季度增加5名患者。APDS patient finding APDS 患者发现As of June 30, 2026, we have identified 1,042 diagnosed APDS patients of all ages globally, including 298 patients in the U.S. and 387 in core markets outside of the U.S. Of the identified patients in the U.S., 198 patients are 12 years of age or older and currently eligible for treatment with Joenja, while 60 are between 4 and 11 years of age.. 截至2026年6月30日，我们在全球范围内已确认1,042名各年龄段的确诊APDS患者，其中包括美国的298名患者以及美国以外核心市场的387名患者。在美国已确认的患者中，198名患者年龄在12岁及以上，目前符合接受Joenja治疗的条件；另有60名患者年龄在4至11岁之间。Joenja (leniolisib) development Joenja（leniolisib）的开发Leniolisib for APDS Leniolisib 用于治疗 APDSAs of June 30, 2026, there are 188 APDS patients in either a leniolisib Expanded Access Program (compassionate use), an ongoing clinical study, or a paid access program. 截至2026年6月30日，共有188名APDS患者参与了leniolisib的扩大访问计划（同情用药）、正在进行的临床研究或付费访问计划。Pediatric label expansion 儿科适应症扩展On June 4, 2026, we announced that the U.S. Food and Drug Administration (FDA) had accepted our resubmitted supplemental New Drug Application (sNDA) seeking approval for Joenja as a treatment for children aged 4 to 11 years with APDS. Following the Complete Response Letter (CRL) received on January 30, 2026, and a subsequent Type A meeting with the FDA on March 26, 2026, the resubmission seeks approval of 40 mg and 50 mg twice-daily dosing for pediatric patients weighing 27 kg or more, who represent a meaningful proportion of the identified pediatric patient population. 2026年6月4日，我们宣布美国食品药品监督管理局（FDA）已受理我们重新提交的补充新药申请（sNDA），该申请旨在寻求批准将Joenja用于治疗4至11岁的活化磷酸肌醇3-激酶δ综合征（APDS）儿童患者。在2026年1月30日收到完全回应函（CRL）并于2026年3月26日与FDA召开A类会议之后，此次重新提交的申请寻求批准对体重为27公斤或以上的儿科患者采用40毫克和50毫克每日两次的给药方案，这类患者占已识别儿科患者群体的相当比例。The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 24, 2026.. 美国食品药品监督管理局（FDA）已根据《处方药用户付费法案》（PDUFA）将目标审批日期定为2026年10月24日。We plan to submit a separate sNDA in the coming days, seeking approval for lower doses in patients weighing 13 - 27 kg. 我们计划在未来几天内提交一份单独的sNDA，寻求批准用于体重在13-27公斤患者的较低剂量。Japan 日本We expect to launch Joenja for the treatment of APDS in adult and pediatric patients aged 4 years and older in the third quarter of 2026. 我们预计将于2026年第三季度推出Joenja，用于治疗4岁及以上成人和儿科患者的APDS。European Economic Area (EEA) 欧洲经济区（EEA）On May 22, 2026, we announced that the European Commission (EC) had granted Marketing Authorization for Joenja as the first and only approved treatment of APDS in adult and pediatric patients 12 years of age and older. Joenja was commercially launched in Germany on July 1, 2026, marking the first European launch following EC approval, with additional launches anticipated pending completion of national reimbursement negotiations.. 2026年5月22日，我们宣布欧盟委员会（EC）已授予Joenja上市许可，使其成为首个且唯一获批用于治疗12岁及以上成人和儿科患者活化磷酸肌醇3-激酶δ综合征（APDS）的药物。Joenja于2026年7月1日在德国正式商业化上市，标志着获得欧盟委员会批准后的首次欧洲上市，随着各国医保报销谈判的完成，预计还将有更多国家陆续上市。Other countries 其他国家On July 8, 2026, Joenja was approved by Health Canada for the treatment of APDS in adult and pediatric patients 12 years of age and older. 2026年7月8日，Joenja获得加拿大卫生部批准，用于治疗12岁及以上成人和儿童患者的活化磷酸肌醇3-激酶δ综合征（APDS）。On July 10, 2026, Joenja was approved by the South Korea Ministry of Food and Drug Safety for the treatment of APDS in adult and pediatric patients 12 years of age and older. 2026年7月10日，Joenja获得韩国食品医药品安全部批准，用于治疗12岁及以上成人和儿科患者的活化磷酸肌醇3-激酶δ综合征（APDS）。Leniolisib for additional primary immunodeficiencies (PIDs) Leniolisib 用于其他原发性免疫缺陷病（PIDs）Two Phase II clinical trials are evaluating leniolisib for additional primary immunodeficiencies (PIDs) with immune dysregulation, including genetically identifiable PIDs linked to altered PI3Kδ signaling and common variable immunodeficiency or CVID, which represent substantially larger patient populations than APDS. 两项II期临床试验正在评估leniolisib在伴有免疫失调的其他原发性免疫缺陷病（PIDs）中的疗效，包括与PI3Kδ信号通路改变相关的可基因鉴定的PIDs以及常见变异型免疫缺陷病（CVID），这些疾病所代表的患者群体规模远大于APDS。Patient enrollment in both clinical trials is complete and we anticipate trial read-outs in the fourth quarter of 2026, consistent with prior guidance. The PI3Kδ pathway is seen as a key driver of immune dysregulation in many PIDs, and we currently anticipate conducting a single registrational Phase III trial in the broader CVID indication, incorporating patient populations from both studies.. 两项临床试验的患者入组工作均已完成，我们预计将于2026年第四季度公布试验结果，与此前指引一致。PI3Kδ通路被视为许多原发性免疫缺陷病（PID）中免疫失调的关键驱动因素，我们目前计划在更广泛的常见变异型免疫缺陷病（CVID）适应症中开展一项单一的注册性III期临床试验，将两项研究中的患者人群纳入其中。A presentation at the 2026 Annual Meeting of the Clinical Immunology Society (CIS), which took place May 6-9, included clinician expanded access experience with leniolisib to treat immune dysregulation in patients with CVID and CVID-like disorders. Clinician-reported outcomes demonstrated improvements, with no progression, in clinical manifestations of immune dysregulation as well as improvements in patients’ quality of life.. 在2026年5月6日至9日举行的临床免疫学会（CIS）年会上，一项报告介绍了医生通过扩大使用途径应用leniolisib治疗常见变异型免疫缺陷病（CVID）及CVID样疾病患者免疫失调的临床经验。医生报告的结果显示，患者的免疫失调临床表现得到改善且无进展，同时患者的生活质量也有所提高。Other events 其他事件As we continue to improve operating efficiency in line with our strategy, we have decided to close our production-support site in Évry, France, with the closure expected to take effect in the fourth quarter of 2026. As a result, we recognized a one-time charge in the current quarter to reflect the estimated costs associated with the planned closure.. 随着我们继续按照战略提高运营效率，我们已决定关闭位于法国埃夫里的生产支持站点，预计该关闭将于2026年第四季度生效。因此，我们在本季度确认了一次性费用，以反映与计划关闭相关的估计成本。Financial Summary 财务摘要Consolidated Statement of Income 合并利润表2Q 2026 2026年第二季度2Q 2025 2025年第二季度1H 2026 2026年上半年1H 2025 2025年上半年Amounts in US$m except per share data 金额单位为百万美元，每股数据除外Total Revenues 总收入90.2 90.293.2 93.2162.7 162.7172.3 172.3Cost of sales 销售成本(14.5) (14.5)(9.0) （9.0）(21.2) (21.2)(17.3) (17.3)Gross profit 毛利75.7 75.784.2 84.2141.5 141.5155.0 155.0Other income 其他收入1.4 1.41.8 1.81.8 1.82.2 2.2Research and development 研发(32.3) (32.3)(23.7) (23.7)(57.8) (57.8)(44.8) (44.8)General and administrative 一般及行政费用(14.9) （14.9）(20.5) (20.5)(30.2) (30.2)(43.0) (43.0)Marketing and sales 市场营销与销售(28.6) (28.6)(31.0) (31.0)(58.9) (58.9)(65.6) (65.6)Other Operating Costs 其他运营成本(75.8) (75.8)(75.2) (75.2)(146.9) (146.9)(153.4) (153.4)Operating profit (loss) 营业利润（亏损）1.3 1.310.8 10.8(3.6) (3.6)3.8 3.8Finance result (net) and share of result in associates 财务业绩（净额）及在联营企业中的损益份额1.8 1.8(3.7) (3.7)1.9 1.9(8.5) (8.5)Profit (loss) before tax 税前利润（亏损）3.0 3.07.1 7.1(1.7) (1.7)(4.7) (4.7)Income tax credit (expense) 所得税抵免（费用）(1.4) (1.4)(2.5) (2.5)(1.9) (1.9)(5.6) (5.6)Profit (loss) for the period 本期利润（亏损）1.6 1.64.6 4.6(3.6) (3.6)(10.3) (10.3)Earnings per share 每股收益Basic, attributable to equity holders of the parent (US$) 基本每股收益，归属于母公司股东（美元）0.003 0.0030.007 0.007(0.005) (0.005)(0.015) (0.015)Diluted, attributable to equity holders of the parent (US$) 稀释后，归属于母公司股东的每股收益（美元）0.002 0.0020.006 0.006(0.005) (0.005)(0.015) (0.015)Segment information - Revenues 分部信息 - 收入2Q 2026 2026年第二季度2Q 2025 2025年第二季度1H 2026 2026年上半年1H 2025 2025年上半年Amounts in US$m 金额（单位：百万美元）Revenue - RUCONEST (US) 收入 - RUCONEST（美国）72.0 72.079.6 79.6130.2 130.2146.2 146.2Revenue - RUCONEST (EU and RoW) 收入 - RUCONEST（欧盟及世界其他地区）0.3 0.30.8 0.80.4 0.42.8 2.8Total Revenues - RUCONEST 总收入 - RUCONEST72.3 72.380.4 80.4130.7 130.7149.0 149.0Revenue - Joenja (US) 收入 - Joenja（美国）15.4 15.411.8 11.826.9 26.921.3 二十一又十分之三Revenue - Joenja (EU and RoW) 收入 - Joenja（欧盟及世界其他地区）2.5 2.51.0 1.05.1 5.12.0 2.0Total Revenues - Joenja 总收入 - Joenja17.9 17.912.8 12.832.0 32.023.3 23.3Total Revenues - US 总收入 - 美国87.4 87.491.4 91.4157.1 157.1167.5 167.5Total Revenues - EU and RoW 总收入 - 欧盟及世界其他地区2.8 2.81.8 1.85.5 5.54.8 4.8Total Revenues 总收入90.2 90.293.2 93.2162.7 162.7172.3 172.3Consolidated Balance Sheet 合并资产负债表June 30, 2026 2026年6月30日December 31, 2025 2025年12月31日Amounts in US$m 金额（单位：百万美元）Cash and cash equivalents, restricted cash and marketable securities 现金及现金等价物、受限现金和有价证券159.5 159.5181.1 181.1Current assets 流动资产280.7 280.7299.5 299.5Total assets 总资产468.0 468.0500.0 五百点零Current liabilities 流动负债93.2 93.2115.8 115.8Shareholders' equity 股东权益270.5 270.5277.1 277.1Figures may not add up due to rounding. 由于四舍五入，各项数字之和可能与总数不符。Financial highlights 财务亮点Second quarter 2026 2026年第二季度For the second quarter of 2026, total revenues decreased by US$3.0 million, or 3%, to US$90.2 million, compared to US$93.2 million in the second quarter of 2025. RUCONEST revenues amounted to US$72.3 million, a 10% decrease compared to the second quarter of 2025. The decrease in RUCONEST® revenues was primarily driven by a decrease in volume. 2026年第二季度，总收入为9,020万美元，较2025年第二季度的9,320万美元减少300万美元，降幅为3%。RUCONEST收入为7,230万美元，较2025年第二季度下降10%。RUCONEST®收入的下降主要源于销量的减少。Joenja revenues amounted to US$17.9 million in the second quarter of 2026, a 40% increase compared to the second quarter of 2025. This increase in Joenja revenues was primarily driven by an increase in volume.. 2026年第二季度，Joenja的营收达到1,790万美元，较2025年第二季度增长40%。Joenja营收的增长主要得益于销量的提升。Gross profit decreased by US$8.5 million, or 10%, to US$75.7 million, compared to US$84.2 million in the second quarter of 2025, mainly due to manufacturing-related impairments of inventory (US$4.9 million) and the decrease in revenues. 毛利润减少了850万美元，即10%，降至7,570万美元，而2025年第二季度为8,420万美元，主要原因是与制造相关的存货减值（490万美元）以及收入下降。The operating profit amounted to US$1.3 million compared to US$10.8 million in the second quarter of 2025. Excluding US$4.9 million in one-time manufacturing-related impairments of inventory and US$1.7 million in expenses associated with the planned closure of the production-support site in Évry, France, adjusted operating profit. 营业利润为130万美元，而2025年第二季度为1,080万美元。若排除与库存相关的一次性制造减值损失490万美元，以及与计划关闭法国埃夫里生产支持站点相关的费用170万美元，调整后营业利润。1 1in the second quarter 2026 amounted to US$7.9 million. Excluding US$2.1 million of non-recurring Abliva acquisition-related expenses, adjusted operating profit in the second quarter 2025 amounted to US$12.9 million. The operating result was primarily impacted by manufacturing-related impairments of inventory and a decrease in revenues, while operating expenses remained similar to the second quarter of 2025.. 2026年第二季度的营业利润为790万美元。剔除与收购Abliva相关的210万美元非经常性费用后，2025年第二季度的调整后营业利润为1290万美元。营业业绩主要受到存货减值（与生产相关）和收入下降的影响，而运营费用与2025年第二季度基本持平。The finance result (net) and share of result in associates amounted to a gain of US$1.8 million compared to a loss of US$3.7 million in the second quarter of 2025. This improvement was mainly driven by favorable EUR/USD exchange rate movements, resulting in a foreign currency gain of US$2.9 million in 2026, compared to a loss of US$1.9 million in the second quarter of 2025.. 财务业绩（净额）及联营公司损益份额为收益180万美元，而2025年第二季度为亏损370万美元。这一改善主要得益于欧元/美元汇率的有利变动，导致2026年实现汇兑收益290万美元，而2025年第二季度则为汇兑损失190万美元。The Company had a net profit of US$1.6 million, compared to US$4.6 million in the second quarter of 2025. The effect of the aforementioned drivers was partially offset by a favorable change in the net finance result. 公司净利润为160万美元，而2025年第二季度为460万美元。上述驱动因素的影响被净财务结果的有利变化部分抵消。Cash used in operations amounted to US$9.7 million, compared to US$11.7 million cash generated from operations in the second quarter of 2025. Cash and cash equivalents, restricted cash and marketable securities decreased from US$171.8 million at the end of first quarter of 2026 to US$159.5 million at the end of the second quarter of 2026, primarily driven by unfavorable working capital movements, mainly a decrease in trade and other payables and an increase in inventories, as well as income tax payments, partially offset by collections of trade and other receivables.. 运营活动使用的现金为970万美元，而2025年第二季度运营活动产生的现金为1,170万美元。现金及现金等价物、受限现金和可流通证券从2026年第一季度末的1.718亿美元减少至2026年第二季度末的1.595亿美元，主要受营运资本不利变动的影响，主要是应付账款和其他应付款项减少以及存货增加，同时还有所得税支付的影响，但部分被应收账款和其他应收款项的收回所抵消。1 1Adjusted Operating Profit is a non-IFRS measure used by management to assess underlying operating performance and provides additional insight into the Company's core operating profitability. It excludes certain non-core items. 经调整经营利润是一项非国际财务报告准则（IFRS）指标，管理层使用该指标评估基础经营业绩，并进一步洞察公司的核心经营盈利能力。该指标剔除了某些非核心项目。First half year 2026 2026年上半年Total revenues decreased 6% during the first half of 2026 to US$162.7 million, compared to US$172.3 million during the first half of 2025. For the first half of 2026, total RUCONEST revenues were 12% lower at US$130.7 million, compared to revenues of US$149.0 million for the first half of 2025. The decrease in RUCONEST revenues was primarily driven by a decrease in volume. 2026年上半年，总收入同比下降6%，至1.627亿美元，而2025年上半年为1.723亿美元。2026年上半年，RUCONEST总收入为1.307亿美元，较2025年上半年的1.490亿美元下降12%。RUCONEST收入下降的主要原因是销量减少。. 。Joenja revenues amounted to US$32.0 million in the first half of 2026, a 37% increase compared to the first half of 2025. This increase in Joenja revenues was primarily driven by an increase in volume. 2026年上半年，Joenja的收入达到3,200万美元，较2025年上半年增长37%。Joenja收入的增长主要得益于销量的增加。Gross profit decreased by US$13.5 million, or 9%, to US$141.5 million, compared to US$155.0 million in the first half of 2025, mainly due to the decrease in revenues and manufacturing-related impairments of inventory (US$4.9 million). Further details on revenue and gross profit segmentation is provided in . 毛利润减少1,350万美元（即9%），至1.415亿美元，而2025年上半年为1.55亿美元，主要原因是收入下降以及与制造相关的存货减值（490万美元）。关于收入和毛利润细分的更多详情见。Note 7. Segment informat 附注7. 分部信息ion 离子in the Notes to the condensed consolidated interim financial statements of this press release. 在本新闻稿的简明合并中期财务报表附注中。The operating loss amounted to US$3.6 million compared to an operating profit of US$3.8 million in the first half of 2025. Excluding US$4.9 million in one-time manufacturing-related impairments of inventory and US$1.7 million in expenses associated with the planned closure of the production-support site in Évry, France, adjusted operating profit in the first half 2026 amounted to US$3.0 million. 营业亏损为360万美元，而2025年上半年营业利润为380万美元。若剔除与存货相关的一次性制造减值490万美元，以及与计划关闭法国埃夫里生产支持站点相关的费用170万美元，2026年上半年的调整后营业利润为300万美元。Excluding US$9.9 million of non-recurring Abliva acquisition-related expenses, adjusted operating profit in the first half 2025 amounted to US$13.7 million. The deteriorated operating result was primarily driven by a decrease in revenues and manufacturing-related impairments of inventories in 2026.. 在剔除990万美元的一次性Abliva收购相关费用后，2025年上半年的调整后营业利润为1,370万美元。经营业绩恶化主要归因于收入下降以及2026年与生产相关的存货减值。The finance result (net) and share result in associates amounted to a gain of US$1.9 million compared to a loss of US$8.5 million in the first half of 2025. This improvement was mainly driven by favorable EUR/USD exchange rate movements, resulting in a foreign currency gain of US$5.3 million in the first half year of 2026, compared to a loss of US$4.5 million in the first half year of 2025.. 财务净结果及联营公司损益合计为收益190万美元，而2025年上半年为亏损850万美元。这一改善主要得益于欧元/美元汇率的有利变动，使得2026年上半年实现汇兑收益530万美元，而2025年上半年则为汇兑损失450万美元。The Company had a net loss of US$3.6 million, compared to a net loss of US$10.3 million in the first half of 2025. In addition to the aforementioned drivers, the net result was positively impacted by a lower tax expense of US$1.9 million compared to US$5.6 million in the first half of 2025. 公司净亏损为360万美元，而2025年上半年的净亏损为1,030万美元。除上述驱动因素外，所得税费用从2025年上半年的560万美元降至190万美元，对净利润产生了正面影响。Cash used in operations amounted to US$7.7 million, compared to US$12.0 million of cash generated from operations in the first half of 2025. Cash and cash equivalents, restricted cash and marketable securities decreased by US$21.6 million to US$159.5 million from US$181.1 million at the end of 2025, primarily driven by negative working capital movements, increased income tax payments and US$12.3 million settlement of the lease liability following the early termination of the DSP facility lease at Pivot Park in Oss, the Netherlands.. 经营所用现金为770万美元，而2025年上半年经营活动产生的现金为1,200万美元。现金及现金等价物、受限现金和有价证券从2025年底的1.811亿美元减少2,160万美元至1.595亿美元，主要受营运资本负面变动、所得税支付增加以及因提前终止位于荷兰奥斯的Pivot Park的DSP设施租赁而结算1,230万美元租赁负债的影响。Outlook/Summary 展望/摘要For 2026, the Company anticipates: 2026年，公司预计：Total revenues between US$375.0 million and US$395.0 million (0% to 5% growth), updated to reflect a US$30 million reduction compared with prior guidance. 总收入介于3.75亿美元至3.95亿美元之间（增长率为0%至5%），已更新以反映较此前指引下调3,000万美元。Total operating expenses between US$315.0 million and US$320.0 million (1% to 3% growth), including over US$40 million incremental R&D investment to advance the pipeline and US$9 million structural G&A cost reductions based on the plan announced in October 2025, reflecting an improvement of US$15 million from prior guidance.. 总运营支出介于3.15亿美元至3.20亿美元之间（增长1%至3%），其中包括为推动产品管线进展而增加的逾4,000万美元研发投资，以及根据2025年10月宣布的计划实现的900万美元结构性一般及行政费用削减，较此前指引改善1,500万美元。RUCONEST revenue stabilization and return to growth during second half of 2026, and significant and accelerating annual Joenja U.S. and ex-U.S. growth. RUCONEST在2026年下半年实现收入稳定并恢复增长，同时Joenja在美国及美国以外地区的年度增长显著且不断加速。Additional regulatory approvals and commercial launches for leniolisib for APDS patients 12 years of age or older and for pediatric label expansion in key global markets. 在关键全球市场，针对12岁及以上活化磷脂酰肌醇3-激酶δ综合征（APDS）患者的leniolisib额外监管审批和商业化发布，以及儿科适应症的标签扩展。Top-line data readouts for the two ongoing leniolisib Phase II clinical trials in PIDs with immune dysregulation, including CVID, to expand the asset’s addressable patient population. 针对两项正在进行的leniolisib治疗免疫失调原发性免疫缺陷病（包括常见变异型免疫缺陷病）的II期临床试验的顶线数据读出，旨在扩大该药物的适用患者人群。Completion of enrollment in the pivotal FALCON clinical study for napazimone (KL1333) in mitochondrial DNA-driven primary mitochondrial diseases. 完成napazimone（KL1333）在由线粒体DNA驱动的原发性线粒体疾病中的关键性FALCON临床研究的入组。Enhancing capital efficiency to drive growth and build a leading global rare disease company. 提升资本效率，驱动增长，打造全球领先的罕见病企业。Continued focus on potential acquisitions and in-licensing of clinical stage opportunities in rare diseases. Financing, if required, would come via a combination of our strong balance sheet and access to capital markets. 持续聚焦于罕见病领域临床阶段项目的潜在收购与许可引进。如需融资，我们将凭借强劲的资产负债表及资本市场渠道相结合的方式进行。No further specific financial guidance for 2026 is provided. 未提供2026年进一步的具体财务指引。Trademarks 商标Joenja® and RUCONEST® are registered trademarks owned by or licensed to Pharming Group N.V. or its affiliates. Joenja® 和 RUCONEST® 是 Pharming Group N.V. 或其关联公司拥有或获许可使用的注册商标。Additional information 附加信息Presentation 演示The conference call presentation is available on the Pharming.com website from 07:30 CEST today. 电话会议演示文稿自今日中欧夏令时 07:30 起可在 Pharming.com 网站上获取。Conference Call 电话会议The conference call will begin at 13:30 CEST/07:30 EDT on Thursday, July 30. A transcript will be made available on the Pharming.com website in the days following the call. 电话会议将于7月30日（星期四）13:30 CEST/07:30 EDT开始。会议记录将在电话会议结束后的几天内发布在Pharming.com网站上。Please note, the Company will only take questions from dial-in attendees. 请注意，公司仅接受通过电话接入的参会者提问。Webcast Link: 网络直播链接：https://edge.media-server.com/mmc/p/m35zejc7 https://edge.media-server.com/mmc/p/m35zejc7Conference call dial-in details: 电话会议拨入详情：https://register-conf.media-server.com/register/BId285845cff504c39931913d279f646ea https://register-conf.media-server.com/register/BId285845cff504c39931913d279f646eaAdditional information on how to register for the conference call/webcast can be found on the 有关如何注册电话会议/网络直播的更多信息，请参见Pharming.com website. Pharming.com 网站。Financial Calendar 2026 2026年财务日历3Q 2026 financial resultsNovember 5, 2026 2026年第三季度财务业绩 2026年11月5日For further public information, contact: 如需更多公开信息，请联系：Pharming 网络钓鱼Michael Levitan, VP Investor Relations and Capital Markets 迈克尔·莱维坦，投资者关系与资本市场副总裁T: +1 (908) 705 1696 电话：+1 (908) 705 1696E: 东：investor@pharming.com investor@pharming.comSaskia Mehring, Head of Corporate Communications 萨斯基亚·梅林，企业传播主管T: +31 6 28 32 60 41 电话：+31 6 28 32 60 41E: 东：media.relations@pharming.com media.relations@pharming.comMedia Relations 媒体关系Julia Deutsch (Lyra Strategic Advisory on behalf of Pharming) 朱莉娅·多伊奇（代表法明公司的莱拉战略咨询）E: 东：JDeutsch@lyraadvisory.com JDeutsch@lyraadvisory.comNetherlands: Leon Melens (LifeSpring Life Sciences Communication on behalf of Pharming) 荷兰：Leon Melens（LifeSpring 生命科学传播公司，代表 Pharming）T: +31 6 53 81 64 27 电话：+31 6 53 81 64 27About Pharming Group N.V. 关于 Pharming Group N.V.Pharming Group N.V. (Euronext Amsterdam: PHARM/Nasdaq: PHAR) is a global biopharmaceutical company dedicated to transforming the lives of patients with rare, debilitating, and life-threatening diseases. We develop and commercialize innovative medicines, including small molecules and biologics. Pharming is headquartered in Leiden, the Netherlands, with U.S. Pharming Group N.V.（泛欧交易所阿姆斯特丹：PHARM/纳斯达克：PHAR）是一家全球性生物制药公司，致力于改善患有罕见、致残及危及生命疾病的患者的生活。我们开发并商业化创新药物，包括小分子药物和生物制品。Pharming 总部位于荷兰莱顿，在美国设有业务。and European operations.. 以及欧洲业务。For more information, visit 更多信息，请访问www.pharming.com www.pharming.comand find us on 并在以下平台找到我们LinkedIn 领英. 。Auditor’s involvement 审计师的参与The Condensed Consolidated Interim Financial Statements have not been audited by the Company’s statutory auditor. 简明合并中期财务报表未经公司法定审计师审计。Responsibility Statement 责任声明The Board of Directors of the Company (the “Board”) hereby declares that to the best of its knowledge, the condensed consolidated interim financial statements, which have been prepared in accordance with IAS 34 (interim financial reporting), give a true and fair view of the assets, liabilities, financial position and profit or loss of the Company, and this interim Board report includes a fair review of the information required pursuant to section 5:25d(8) and (9) of the Dutch Financial Supervision Act (Wet op het financieel toezicht). 本公司董事会（“董事会”）谨此声明，据其所知，按照《国际会计准则第34号——中期财务报告》编制的简明合并中期财务报表真实、公允地反映了本公司的资产、负债、财务状况及损益情况；且本中期董事会报告包含了对根据《荷兰金融监管法》（Wet op het financieel toezicht）第5:25d条第(8)款和第(9)款规定所需信息的公允审阅。. 。Leiden, July 30, 2026 莱顿，2026年7月30日Fabrice Chouraqui, Chief Executive Officer and Executive Director 法布里斯·肖拉基，首席执行官兼执行董事Richard Peters, Non-Executive Director and Chairman of the Board of Directors 理查德·彼得斯，非执行董事兼董事会主席Mark Pykett, Non-Executive Director 马克·皮凯特，非执行董事Barbara Yanni, Non-Executive Director 芭芭拉·雅尼，非执行董事Leonard Kruimer, Non-Executive Director 伦纳德·克鲁伊默，非执行董事Jabine van der Meijs, Non-Executive Director 贾宾·范德梅斯，非执行董事Elaine Sullivan, Non-Executive Director 伊莱恩·沙利文，非执行董事Forward-looking Statements 前瞻性陈述This press release may contain forward-looking statements. Forward-looking statements are statements of future expectations that are based on management’s current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in these statements. 本新闻稿可能包含前瞻性陈述。前瞻性陈述是关于未来预期的陈述，基于管理层当前的预期和假设，并涉及已知和未知的风险与不确定性，这些风险与不确定性可能导致实际结果、业绩或事件与这些陈述中明示或暗示的内容存在重大差异。These forward-looking statements are identified by their use of terms and phrases such as “aim”, “ambition”, ‘‘anticipate’’, ‘‘believe’’, ‘‘could’’, ‘‘estimate’’, ‘‘expect’’, ‘‘goals’’, ‘‘intend’’, ‘‘may’’, “milestones”, ‘‘objectives’’, ‘‘outlook’’, ‘‘plan’’, ‘‘probably’’, ‘‘project’’, ‘‘risks’’, “schedule”, ‘‘seek’’, ‘‘should’’, ‘‘target’’, ‘‘will’’ and similar terms and phrases. 这些前瞻性陈述通过使用诸如“目标”、“雄心”、“预期”、“相信”、“可能”、“估计”、“期望”、“目的”、“打算”、“可以”、“里程碑”、“指标”、“展望”、“计划”、“或许”、“预测”、“风险”、“时间表”、“寻求”、“应当”、“靶点”、“将会”等词语和短语以及类似表述来识别。Examples of forward-looking statements may include statements with respect to timing and progress of Pharming's preclinical studies and clinical trials of its product candidates, Pharming's clinical and commercial prospects, and Pharming's expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharming's clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory, commercial, competitive and technical developments. 前瞻性陈述的示例可能包括有关Pharming公司候选产品临床前研究和临床试验的时间安排和进展的陈述、Pharming公司的临床和商业前景，以及Pharming公司对其预计营运资金需求和现金资源的预期。这些陈述受多种风险、不确定性和假设的影响，包括但不限于Pharming公司临床试验的范围、进展和扩展及其对成本的影响；以及临床、科学、监管、商业、竞争和技术发展等方面的因素。In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's. 鉴于这些风险与不确定性，以及Pharming公司所描述的其他风险与不确定性。2025 2025年Annual Report and the Annual Report on Form 20-F for the year ended December 31, 截至12月31日年度的年度报告及20-F表格年度报告2025, 2025年，filed with the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forward-looking statements may not occur, and Pharming's actual results could differ materially and adversely from those anticipated or implied thereby. All forward-looking statements contained in this press release are expressly qualified in their entirety by the cautionary statements contained or referred to in this section. 已向美国证券交易委员会备案，此类前瞻性陈述中讨论的事件和情况可能不会发生，Pharming 的实际结果可能与由此预期或暗示的结果存在重大且不利的差异。本新闻稿中包含的所有前瞻性陈述均受本节所载或提及的警示性陈述的明确限定，其全部内容由这些警示性陈述予以限定。Readers should not place undue reliance on forward-looking statements. Any forward-looking statements speak only as of the date of this press release and are based on information available to Pharming as of the date of this release. Pharming does not undertake any obligation to publicly update or revise any forward-looking statement as a result of new information, future events or other information.. 读者不应过度依赖前瞻性陈述。任何前瞻性陈述仅反映本新闻稿发布之日的情况，并基于Pharming在该日期可获得的信息。Pharming不承担因新信息、未来事件或其他信息而公开更新或修订任何前瞻性陈述的义务。Inside Information 内幕信息This press release relates to the disclosure of information that qualifies, or may have qualified, as inside information within the meaning of Article 7(1) of the EU Market Abuse Regulation. 本新闻稿涉及披露根据《欧盟市场滥用条例》第7(1)条的定义，构成或可能构成内幕信息的信息。Pharming Group N.V. 法明集团 N.V.Condensed Consolidated Interim Financial Statements in US Dollars (unaudited) 美元简明合并中期财务报表（未经审计）For the period ended June30, 2026 截至2026年6月30日止期间Condensed consolidated interim statement of income 简明合并中期利润表Condensed consolidated interim statement of comprehensive income 简明合并中期综合收益表Condensed consolidated interim balance sheet 简明合并中期资产负债表Condensed consolidated interim statement of changes in equity 简明合并中期权益变动表Condensed consolidated interim statement of cash flow 简明合并中期现金流量表CONDENSED CONSOLIDATED INTERIM STATEMENT OF INCOME (UNAUDITED) 简明合并中期利润表（未经审计）For the period ended June 30 截至6月30日的期间Amounts in US$ ‘000 金额（千美元）notes 笔记1H 2026 2026年上半年1H 2025 2025年上半年Revenues 收入7 7162,660 162,660172,315 172,315Costs of sales 销售成本9 九(21,189) (21,189)(17,295) (17,295)Gross profit 毛利润7 7141,471 141,471155,020 155,020Other income 其他收入8 81,801 1,8012,232 2,232Research and development 研发(57,819) (57,819)(44,837) (44,837)General and administrative 一般及行政(30,165) (30,165)(42,991) (42,991)Marketing and sales 营销与销售(58,886) (58,886)(65,619) (65,619)Other Operating Costs 其他运营成本9 9(146,870) (146,870)(153,447) (153,447)Operating profit (loss) 营业利润（亏损）(3,598) (3,598)3,805 3,805Other finance income 其他财务收入10 107,119 7,1191,263 1,263Other finance expenses 其他财务费用10 10(5,403) (5,403)(9,785) (9,785)Finance result, net 财务结果，净额1,716 1,716(8,522) (8,522)Share of net profits (loss) in associates using the equity method 采用权益法核算的联营企业净利润（亏损）份额12 十二168 一百六十八8 8Profit (loss) before tax 税前利润（亏损）(1,714) (1,714)(4,709) (4,709)Income tax credit (expense) 所得税抵免（费用）11 十一(1,861) (1,861)(5,629) (5,629)Profit (loss) for the period 本期利润（亏损）(3,575) (3,575)(10,338) (10,338)Attributable to: 归因于：Equity holders of the parent 母公司股东(3,575) (3,575)(10,025) (10,025)Non-controlling interests 非控制性权益— —(313) (313)Earnings per share 每股收益Basic earnings per share (US$) 基本每股收益（美元）18 十八(0.005) (0.005)(0.015) (0.015)Diluted earnings per share (US$) 稀释每股收益（美元）18 十八(0.005) (0.005)(0.015) (0.015)CONDENSED CONSOLIDATED INTERIM STATEMENT OF COMPREHENSIVE INCOME (UNAUDITED) 简明合并中期综合收益表（未经审计）For the period ended June 30 截至6月30日的期间Amounts in US$ ‘000 金额（千美元）1H 2026 2026年上半年1H 2025 2025年上半年Profit (loss) for the period 本期利润（亏损）(3,575) (3,575)(10,338) (10,338)Currency translation differences 货币折算差异(8,433) (8,433)26,148 26,148Items that may be subsequently reclassified to profit or loss 可能随后重分类至损益的项目(8,433) (8,433)26,148 26,148Other comprehensive income (loss), net of tax 其他综合收益（损失），税后净额(8,433) (8,433)26,148 26,148Total comprehensive income (loss) for the period 本期综合收益（亏损）总额(12,008) (12,008)15,810 15,810Attributable to: 归因于：Equity holders of the parent 母公司股东(12,008) (12,008)16,123 16,123Non-controlling interests 非控制性权益— —(313) (313)CONDENSED CONSOLIDATED INTERIM BALANCE SHEET (UNAUDITED) 简明合并中期资产负债表（未经审计）Amounts in US$ ‘000 金额（千美元）notes 笔记June 30, 2026 2026年6月30日December 31, 2025 2025年12月31日Non-current assets 非流动资产Intangible assets 无形资产128,082 128,082135,538 135,538Property, plant and equipment 物业、厂房及设备6,425 6,4257,233 7,233Right-of-use assets 使用权资产14,058 14,05816,738 16,738Long-term prepayments 长期预付款项92 九十二94 九十四Deferred tax assets 递延所得税资产13 1328,838 28,83831,017 三万一千零一十七Investment accounted for using the equity method 采用权益法核算的投资12 122,055 2,0551,944 1,944Investment in debt instruments designated as at FVTPL 指定为以公允价值计量且其变动计入当期损益的债务工具投资12 126,520 6,5206,703 6,703Restricted cash 受限现金1,225 一千二百二十五1,227 1,227Total non-current assets 非流动资产总额187,295 187,295200,495 200,495Current assets 流动资产Inventories 存货14 十四65,428 65,42864,902 64,902Trade and other receivables 贸易及其他应收款项56,980 56,98054,704 54,704Restricted cash 受限现金— —761 761Marketable securities 有价证券15 15— —33,796 33,796Cash and cash equivalents 现金及现金等价物15 15158,281 158,281145,305 145,305Total current assets 流动资产总额280,689 280,689299,469 299,469Total assets 总资产467,984 467,984499,963 499,963Equity 股权Share capital 股本8,081 8,0818,009 8,009Share premium 股本溢价520,312 520,312513,257 513,257Other reserves 其他储备20,342 20,34228,819 28,819Accumulated deficit 累计亏损(278,245) (278,245)(272,983) (272,983)Total equity 股东权益总额16 16270,490 270,490277,102 277,102Non-current liabilities 非流动负债Convertible bonds 可转换债券17 1792,401 九万两千四百零一92,719 九万二千七百一十九Lease liabilities 租赁负债11,848 11,84814,351 一万四千三百五十一Total non-current liabilities 非流动负债总额104,249 104,249107,070 107,070Current liabilities 流动负债Convertible bonds 可转换债券17 十七5,469 5,4695,336 5,336Provisions 条款1,878 1,8781,187 1,187Trade and other payables 贸易及其他应付款项82,321 82,321105,899 105,899Lease liabilities 租赁负债3,577 3,5773,369 3,369Total current liabilities 流动负债总额93,245 93,245115,791 115,791Total equity and liabilities 权益和负债总额467,984 467,984499,963 499,963CONDENSED CONSOLIDATED INTERIM STATEMENT OF CHANGES IN EQUITY (UNAUDITED) 简明合并中期权益变动表（未经审计）For the period ended June 30 截至6月30日的期间Attributable to equity holders of the parent 归属于母公司股东Amounts in US$ ‘000 金额（千美元）notes 笔记Share capital 股本Share premium 股本溢价Other reserves 其他储备Accumulated deficit 累计亏损Subtotal 小计Non-controlling interests 非控制性权益Total equity 股东权益总额Balance at January 1, 2025 2025年1月1日余额7,769 7,769488,990 488,990(209) (209)(275,489) (275,489)221,061 221,061— —221,061 221,061Profit (loss) for the period 本期利润（亏损）— —— —— —(10,025) (10,025)(10,025) (10,025)(313) （313）(10,338) (10,338)Other comprehensive income (loss) for the period 本期其他综合收益（损失）— —— —26,148 26,148— —26,148 26,148— —26,148 26,148Total comprehensive income (loss) for the period 本期综合收益（亏损）总额— —— —26,148 26,148(10,025) (10,025)16,123 16,123(313) (313)15,810 15,810Movement in reserves 准备金变动16 十六— —— —(31) (31)31 三十一— —— —— —Income tax benefit from excess tax deductions related to share-based payments 与股份支付相关的超额税收扣除所产生的所得税收益— —— —— —(209) （209）(209) (209)— —(209) (209)Share-based compensation 基于股份的薪酬— —— —— —6,052 6,0526,052 六千零五十二— —6,052 6,052Options exercised / LTIP shares issued 已行权期权 / 长期激励计划股份发行52 五十二2,863 2,863— —(4,273) (4,273)(1,358) (1,358)— —(1,358) (1,358)Acquisition of a subsidiary 收购子公司— —— —— —— —— —6,133 6,1336,133 6,133Acquisition of non-controlling interests 收购非控制性权益— —— —— —(2,118) (2,118)(2,118) (2,118)(5,820) (5,820)(7,938) (7,938)Total transactions with owners, recognized directly in equity 与所有者进行的总交易，直接计入权益52 五十二2,863 2,863(31) (31)(517) （517）2,367 2,367313 三百一十三2,680 2,680Balance at June 30, 2025 截至2025年6月30日的余额7,821 7,821491,853 491,85325,908 25,908(286,031) (286,031)239,551 239,551— —239,551 239,551Balance at January 1, 2026 2026年1月1日余额8,009 8,009513,257 513,25728,819 28,819(272,983) (272,983)277,102 277,102— —277,102 277,102Profit (loss) for the period 本期利润（亏损）— —— —— —(3,575) (3,575)(3,575) (3,575)— —(3,575) (3,575)Other comprehensive income (loss) for the period 当期其他综合收益（损失）— —— —(8,433) (8,433)— —(8,433) (8,433)— —(8,433) (8,433)Total comprehensive income (loss) for the period 本期综合收益总额（亏损）— —— —(8,433) (8,433)(3,575) (3,575)(12,008) (12,008)— —(12,008) (12,008)Movement in reserves 准备金变动16 16— —— —(44) (44)34 三十四(10) (10)— —(10) (10)Income tax expense from excess tax deductions related to share-based payments 与股份支付相关的超额税收抵扣所产生的所得税费用— —— —— —248 二百四十八248 二百四十八— —248 248Share-based compensation 基于股份的薪酬— —— —— —6,575 6,5756,575 6,575— —6,575 6,575Options exercised / LTIP shares issued 行使期权 / 发行长期激励计划股份71 717,056 7,056— —(8,545) (8,545)(1,418) (1,418)— —(1,418) (1,418)Total transactions with owners, recognized directly in equity 与所有者之间的交易总额，直接计入权益71 七十一7,056 七千零五十六(44) (44)(1,688) (1,688)5,395 5,395— —5,395 5,395Balance at June 30, 2026 截至2026年6月30日的余额8,081 8,081520,312 520,31220,342 20,342(278,245) (278,245)270,490 270,490— —270,490 270,4902 2Comparative presentation updated for consistency. 比较列报已更新以保持一致性。CONDENSED CONSOLIDATED INTERIM STATEMENT OF CASH FLOWS (UNAUDITED) 简明合并中期现金流量表（未经审计）For the period ended June 30 截至6月30日的期间Amounts in $’000 金额单位：千美元1H 2026 2026年上半年1H 2025 2025年上半年Profit (loss) before tax 税前利润（亏损）(1,714) (1,714)(4,709) (4,709)Adjustments to reconcile net profit (loss) to net cash used in operating activities: 将净利润（亏损）调节为经营活动产生的现金流量净额的调整项目：Depreciation, amortization, impairment of non-current assets 折旧、摊销及非流动资产减值6,154 6,1545,284 5,284Equity settled share based payments 以权益结算的股份支付6,575 6,5756,052 6,052Loss (gain) on disposal of leases 租赁处置损益38 三十八(10) （10）Impairments of inventories² 存货减值²5,990 5,9903,742 3,742Other finance income 其他财务收入(7,119) (7,119)(1,263) (1,263)Other finance expenses 其他财务费用5,371 5,3719,650 9,650Share of net losses (gains) in associates using the equity method 按权益法核算的联营企业净亏损（收益）份额(168) (168)(8) (8)Operating cash flows before changes in working capital 营运资本变动前的经营现金流15,127 15,12718,738 18,738Changes in working capital: 营运资本变动：Inventories² 存货²(7,256) (7,256)(4,051) (4,051)Trade and other receivables 贸易及其他应收款项1,320 1,3202,359 2,359Payables and other current liabilities 应付账款及其他流动负债(13,159) (13,159)1,031 1,031Provisions 条款691 六百九十一— —Restricted cash 受限现金709 709(3,052) (3,052)Total changes in working capital 营运资本总变动(17,695) (17,695)(3,713) (3,713)Interest received 收到的利息1,266 1,2661,273 1,273Income taxes received (paid) 收到（支付）的所得税(6,404) (6,404)(4,323) (4,323)Net cash flows generated from (used in) operating activities 经营活动产生的（用于）净现金流量(7,706) (7,706)11,975 11,975Capital expenditure for property, plant and equipment 物业、厂房及设备的资本支出(321) (321)(410) (410)Investment intangible assets 投资性无形资产— —(6) (6)Investment in associates using the equity method 采用权益法核算的联营企业投资— —(429) (429)Purchases of marketable securities 有价证券的购买(102,646) (102,646)— —Proceeds from sale of marketable securities 出售有价证券所得款项18,124 18,12484,967 84,967Acquisition of a subsidiary, net of cash acquired 收购子公司，扣除所获现金— —(57,476) (57,476)Net cash flows generated from (used in) investing activities 投资活动产生的（用于）净现金流量(84,843) (84,843)26,646 26,646Payment of lease liabilities 租赁负债的支付(13,894) (13,894)(1,781) (1,781)Interests on lease liabilities 租赁负债利息(242) (242)(562) (562)Interests on convertible bonds 可转换债券的利息(2,630) (2,630)(2,450) (2,450)Exercise of share-based compensation awards 行使基于股份的薪酬奖励5,098 5,0981,287 1,287Acquisition of non-controlling interests 收购非控股权益— —(5,970) (5,970)Net cash flows generated from (used in) financing activities 筹资活动产生的（用于）现金流量净额(11,668) (11,668)(9,476) (9,476)Increase (decrease) of cash 现金增加（减少）额(104,217) (104,217)29,145 29,145Exchange rate effects 汇率影响(603) (603)8,002 8,002Effect of reclassification of money market funds to cash equivalents (see note 15) 货币市场基金重分类为现金等价物的影响（见附注15）117,796 117,796— —Cash and cash equivalents at January 1 1月1日的现金及现金等价物145,305 145,30554,944 54,944Total cash and cash equivalents at June 30 截至6月30日的现金及现金等价物总额158,281 158,28192,091 92,091Notes to the condensed consolidated interim financial statements 简明合并中期财务报表附注For the period ended June30, 2026 截至2026年6月30日止期间1. 1.Company information 公司信息Pharming Group N.V. is a limited liability public company which is listed on Euronext Amsterdam (PHARM) and on the NASDAQ (PHAR), with its headquarters and registered office located at: Pharming Group N.V. 是一家有限责任公司，在阿姆斯特丹泛欧交易所（PHARM）和纳斯达克（PHAR）上市，其总部和注册办公地点位于：Darwinweg 24 达尔文路24号2333 CR Leiden 2333 CR 莱顿The Netherlands 荷兰Pharming Group N.V. is a global biotechnology company that develops and commercializes innovative therapies for rare and ultra-rare diseases with significant unmet need. We focus on immunological and genetic conditions where our scientific and commercial expertise can help advance care over the long term.. Pharming Group N.V. 是一家全球性生物技术公司，致力于开发并商业化创新疗法，以满足罕见病和超罕见病领域尚未被满足的重大医疗需求。我们专注于免疫学和遗传性疾病，凭借我们的科学与商业专长，推动长期护理水平的提升。2. 2.Statement of compliance 合规声明The consolidated interim financial statements for the six-month period ended June30, 2026, have been prepared in accordance with International Accounting Standard IAS 34, Interim financial reporting. The condensed consolidated interim financial statements should be read in conjunction with the annual financial statements for the year ended December31, 2025. 截至2026年6月30日止六个月期间的合并中期财务报表已根据《国际会计准则第34号——中期财务报告》编制。简明合并中期财务报表应与截至2025年12月31日止年度的年度财务报表一并阅读。They do not include all of the information required for a complete set of financial statements in accordance with IFRS Accounting Standards. However, selected explanatory notes are included to explain events and transactions that are significant to an understanding of the changes in the Group’s financial position and performance since the last annual financial statements.. 这些报表并未包含根据《国际财务报告准则》（IFRS）编制完整财务报表所需的全部信息。然而，其中包含了部分选定的附注，以解释对于理解本集团自上一份年度财务报表以来财务状况和经营成果的变化具有重大影响的事项和交易。These condensed consolidated interim financial statements were authorized for issue by the Board of Directors on July29, 2026. 这些简明合并中期财务报表已于2026年7月29日经董事会批准发布。The published figures in these condensed consolidated interim financial statements are unaudited. 这些简明合并中期财务报表中公布的数字未经审计。3. 3.Accounting policies 会计政策Accounting policies are consistent with those of the financial statements for the year ended December31, 2025. The following exchange rates have been applied: 会计政策与截至2025年12月31日止年度的财务报表所采用的会计政策保持一致。已应用以下汇率：Applied exchange rates 适用汇率June 30, 2026 2026年6月30日Average 1H 2026 2026年上半年平均December 31, 2025 2025年12月31日Average 1H 2025 2025年上半年平均值EUR/USD 欧元/美元1.1394 1.13941.1687 1.16871.1713 1.17131.0889 1.0889AUD/USD 澳元/美元0.6887 0.68870.7017 0.70170.6699 0.66990.6322 0.6322GBP/USD 英镑/美元1.3221 1.32211.3458 1.34581.3455 1.34551.2992 1.2992SEK/USD 瑞典克朗/美元0.1027 0.10270.1084 0.10840.1083 0.10830.0981 0.09814. 4.Estimates and judgements 估计与判断The preparation of interim financial statements in conformity with IAS 34 and Book 2 Title 9 of the Dutch Civil Code requires the use of certain critical accounting estimates. It also requires management to exercise its judgement in the process of applying the Company’s accounting policies. In preparing these condensed consolidated interim financial statements, the significant judgements made by management in applying the Company’s accounting policies were the same as those applied to the consolidated financial statements for the year ended December31, 2025.. 根据《国际会计准则第34号》和《荷兰民法典》第二编第九标题的规定编制中期财务报表，需要使用某些关键的会计估计。此外，还要求管理层在应用公司会计政策的过程中行使判断力。在编制这些简明合并中期财务报表时，管理层在应用公司会计政策方面所作出的重大判断与应用于截至2025年12月31日止年度的合并财务报表中的判断一致。5. 5.Going concern 持续经营In preparing and finishing the interim financial statements the Board of Directors of Pharming have assessed the Company’s ability to fund its operations for a period of at least twelve months after the date the interim financial statements are issued. Based upon the assessment on a going concern basis, the Company has concluded that funding of its operations for a period of twelve months, after the date the interim financial statements are issued, is realistic and achievable. 在编制和完成中期财务报表时，Pharming公司董事会已评估了公司自中期财务报表发布之日起至少十二个月内为其运营提供资金的能力。基于持续经营假设进行的评估，公司得出结论：自中期财务报表发布之日起十二个月内为其运营提供资金是现实且可实现的。Overall, based on the outcome of this assessment, the interim financial statements have been prepared on a going concern basis.. 总体而言，根据本次评估的结果，中期财务报表系以持续经营为基础编制。6. 6.Seasonality of operations 运营的季节性Seasonality has no material impact on Company’s interim financial statements. 季节性因素对公司中期财务报表无重大影响。7. 7.Segment information 分部信息Operating segments are components of the Company that engage in business activities from which it may incur expenses, for which discrete financial information is available and whose operating results are evaluated regularly by the Company’s Chief Operating Decision Maker (“CODM”) to make decisions about resources to be allocated to the segment and assess its performance. 经营分部是指公司内从事业务活动的组成部分，这些活动可能产生费用，且有独立的财务信息可供使用，公司的首席运营决策者（“CODM”）会定期评估其经营成果，以决定分配给该分部的资源并评估其绩效。The Executive Members of the Board of Directors are considered the CODM.. 董事会的执行成员被视为首席运营决策者（CODM）。CODM reviews the Company’s results under four operating segments based on a combination of the products that the Company has launched - RUCONEST and Joenja, and the main geographies where sales are consummated - focused on the US and reporting, in aggregate, EU and Rest of the World (“RoW”). The four operating segments correspond to each of its four reportable segments for financial reporting purposes.. 首席运营决策者根据公司已推出的产品（RUCONEST 和 Joenja）以及销售完成的主要地理区域（聚焦于美国，并将欧盟和世界其他地区（“RoW”）合并列报）的组合，对公司的业绩按四个经营分部进行审查。这四个经营分部分别对应其用于财务报告目的的四个报告分部。The CODM reviews revenues and gross profit to assess the performance of their operating segments, which are the sole performance measures on segment level which are provided regularly to the CODM. No other information, such as operating expenses, assets or other performance indicators on segment level are provided regularly to the CODM. 首席运营决策者（CODM）通过审查收入和毛利来评估其经营分部的业绩，这些是定期向首席运营决策者提供的唯一分部层面业绩指标。其他信息，如分部层面的运营费用、资产或其他业绩指标，并不定期向首席运营决策者提供。. 。Total revenues and gross profit per each operating and reportable segment for the period ended June 30 are: 截至6月30日止期间，各经营及可报告分部的总收入和毛利如下：Amounts in US$ ‘000 金额（千美元）1H 2026 2026年上半年1H 2025 2025年上半年RUCONEST RUCONESTJoenja 乔恩贾Total 总计RUCONEST RUCONESTJoenja 乔恩贾Total 总计Revenues: 收入：US 美国130,225 130,22526,944 26,944157,169 157,169146,244 146,24421,272 21,272167,516 167,516EU and RoW 欧盟与世界其他地区439 四百三十九5,052 5,0525,491 5,4912,759 2,7592,040 2,0404,799 4,799Total revenues 总收入130,664 130,66431,996 31,996162,660 162,660149,003 149,00323,312 23,312172,315 172,315Gross profit: 毛利润：US 美国112,971 112,97123,472 23,472136,443 136,443134,211 134,21118,448 18,448152,659 152,659EU and RoW 欧盟及世界其他地区176 1764,852 4,8525,028 5,028340 三百四十2,021 2,0212,361 2,361Total gross profit 毛利总额113,147 113,14728,324 28,324141,471 141,471134,551 134,55120,469 20,469155,020 155,020There are no intersegment sales. 不存在分部间销售。8. 8.Other income 其他收入Other income decreased by US$0.4 million in the first half of 2026 to US$1.8 million as compared to US$2.2 million the first half of 2025. 2026年上半年，其他收入为180万美元，较2025年上半年的220万美元减少40万美元。9. 9.Expenses by nature 按性质分类的费用Costs of sales 销售成本Amounts in US$ ‘000 金额（单位：千美元）1H 2026 2026年上半年1H 2025 2025年上半年Cost of inventories recognized as expenses 确认为费用的存货成本(12,681) (12,681)(13,199) (13,199)Royalty fees 特许权使用费(3,361) (3,361)(2,421) (2,421)Inventory impairments 存货减值(5,147) (5,147)(1,675) (1,675)Total 总计(21,189) (21,189)(17,295) (17,295)Costs of inventories recognized as expenses in the first half year of 2026 were US$12.7 million versus US$13.2 million for the first half of 2025 and relates to actual product sales of RUCONEST and Joenja. 2026年上半年确认为费用的存货成本为1,270万美元，而2025年同期为1,320万美元，这与RUCONEST和Joenja的实际产品销售相关。Pharming expensed royalty fees to Novartis on Joenja sales, amounting to US$3.4 million in the first half of 2026 (first half of 2025: US$2.4 million). Pharming将Joenja销售相关的特许权使用费计入费用，支付给诺华，2026年上半年金额为340万美元（2025年上半年：240万美元）。Inventory impairments amounted to US$5.1 million (1H 2025: US$1.7 million) and stems from the valuation of the inventories against lower net realizable value and mainly relates to material no longer expected to be used for commercial sales. 存货减值金额为510万美元（2025年上半年：170万美元），源于按较低的净可变现价值对存货进行估值，主要涉及预计不再用于商业销售的材料。Other operating costs 其他运营成本Other operating costs decreased to US$146.9 million in the first half of 2026 compared to US$153.4 million in the first half year of 2025. 其他运营成本从2025年上半年的1.534亿美元下降至2026年上半年的1.469亿美元。Employee benefits are charged to research and development costs, general and administrative costs, or marketing and sales costs based on the nature of the services provided. Employee benefits of production related employees have been included in the value of inventories. 员工福利根据所提供服务的性质，计入研发费用、一般及管理费用或营销及销售费用。与生产相关的员工福利已计入存货价值。Depreciation and amortization charges amounted to US$6.0 million in the first half of 2026 compared to US$5.3 million the first half year of 2025, and related to the following: 2026年上半年，折旧和摊销费用为600万美元，而2025年上半年为530万美元，具体涉及以下项目：Amounts in US$ ‘000 金额（单位：千美元）1H 2026 2026年上半年1H 2025 2025年上半年Property, plant and equipment 物业、厂房及设备(616) (616)(650) (650)Right-of-use assets 使用权资产(1,494) (1,494)(1,475) (1,475)Intangible assets 无形资产(3,860) (3,860)(3,159) (3,159)Total 总计(5,970) (5,970)(5,284) (5,284)10. 10.Finance income (expenses) 财务收入（费用）Amounts in US$ ‘000 金额（单位：千美元）1H 2026 2026年上半年1H 2025 2025年上半年Foreign currency results 外币结果5,303 5,303— —Interest income 利息收入1,816 1,8161,263 一千二百六十三Other finance income 其他财务收入7,119 7,1191,263 1,263Foreign currency results 外币业绩— —(4,549) (4,549)Fees and expenses on repayment and issuance convertible bonds 可转换债券发行及偿还相关的手续费和支出— —— —Amortization and interest on convertible bonds 可转换债券的摊销与利息(5,179) (5,179)(4,586) (4,586)Interest leases 利息租赁(192) (192)(516) （516）Other finance expenses 其他财务费用(32) (32)(136) (136)Other finance expenses 其他财务费用(5,403) (5,403)(9,787) (9,787)Total other finance income and expenses 其他财务收支总额1,716 1,716(8,524) (8,524)Foreign currency results primarily reflect movements in the EUR/USD exchange rate. The strengthening of the U.S. dollar against the euro during the first half of 2026 (compared with a weakening during the first half of 2025) generated foreign exchange gains. These gains were mainly attributable to the revaluation of the U.S. 外币业绩主要反映欧元/美元汇率的变动。2026年上半年美元兑欧元走强（而2025年上半年则为走弱），由此产生汇兑收益。这些收益主要 attributable to 美国的重新估值。dollar-denominated cash and marketable securities balances held by euro functional currency entities and euro-denominated monetary assets and liabilities held by the U.S. dollar functional currency entity.. 以欧元为功能货币的实体持有的美元现金及有价证券余额，以及以美元为功能货币的实体持有的欧元货币性资产和负债。Interest income increased compared with the first half of 2025 due to a higher average balance of cash and marketable securities following the completion of the Abliva acquisition in the first half of 2025, as well as higher effective yields earned on cash and cash equivalents. 利息收入较2025年上半年有所增加，原因是2025年上半年完成对Abliva的收购后，现金及有价证券的平均余额上升，同时现金及现金等价物的实际收益率也有所提高。11. 11.Income tax (expenses) 所得税（费用）Income tax expenses are recognized in each interim period based on the best estimate of the weighted average annual effective income tax rate expected for the full financial year. 所得税费用根据对整个财务年度预期的加权平均年有效所得税率的最佳估计，在每个中期期间确认。12. 12.Investments 投资Investments accounted for using the equity method 采用权益法核算的投资The asset relates to an investment in the ordinary shares of BioConnection Investments B.V. (“BioConnection”). In the Board of Directors’ judgement, the investment in BioConnection constitutes an investment in an associated company and is therefore not consolidated. Pharming has significant influence but does not have control of BioConnection and is embargoed by a shareholder’s agreement between the shareholders of BioConnection from influencing any activity between the two parties which is in any significant way different from the relationship which existed between the two prior to the investment.. 该资产涉及对 BioConnection Investments B.V.（“BioConnection”）普通股的投资。董事会认为，对 BioConnection 的投资构成对联营公司的投资，因此不纳入合并报表范围。Pharming 对 BioConnection 具有重大影响，但并未取得控制权；同时，根据 BioConnection 股东之间的股东协议，Pharming 被禁止影响双方之间任何与投资前既存关系存在显著差异的活动。The carrying amount of this investment has changed as follows: 该项投资的账面价值变动如下：Amounts in US$ ‘000 金额以千美元计Period to June 30, 2026 截至2026年6月30日的期间Period to December 31, 2025 截至2025年12月31日的期间Balance at January 1 1月1日余额1,944 1,944466 四百六十六Share in net profit (loss) for the period 本期净利润（亏损）份额168 168623 六百二十三Equity contribution 股权出资— —739 七百三十九Currency translation 货币折算(57) (57)116 一百一十六Balance at end of period 期末余额2,055 两千零五十五1,944 1,944Investment in debt instruments designated as at FVTPL 指定为以公允价值计量且其变动计入当期损益的债务工具投资The asset relates to the preference share in BioConnection Investments B.V. The Board of Directors made an assessment on the accounting treatment of the preference share obtained. The Board concluded that the asset should be recognized as a financial asset (debt instrument) measured at initial recognition at fair value, subsequently measured at fair value through profit and loss. 该资产涉及 BioConnection Investments B.V. 的优先股。董事会对取得的优先股的会计处理进行了评估。董事会得出结论，该资产应确认为金融资产（债务工具），在初始确认时以公允价值计量，后续以公允价值计量且其变动计入当期损益。The fair value is calculated on a yearly basis using the forward-looking Black-Scholes-Merton (“BSM”) financial instrument pricing framework. No events or matters are known as of the date of this report which would lead to a significant impact in the fair value of the asset, compared to December31, 2025.. 公允价值采用前瞻性的布莱克-斯科尔斯-默顿（“BSM”）金融工具定价框架按年度计算。截至本报告日期，未发现任何会导致资产公允价值相较于2025年12月31日发生重大变动的事件或事项。The carrying amount of this investment has changed as follows: 该项投资的账面价值变动如下：Amounts in US$ ‘000 金额（千美元）Period to June 30, 2026 截至2026年6月30日的期间Period to December 31, 2025 截至2025年12月31日的期间Balance at January 1 1月1日余额6,703 6,7033,767 3,767Fair value changes 公允价值变动— —2,345 2,345Currency translation 货币折算(183) (183)591 五百九十一Balance at end of period 期末余额6,520 6,5206,703 6,70313. 13.Deferred tax assets 递延所得税资产The deferred tax assets decreased mainly due to foreign exchange effects and changes in temporary differences. 递延所得税资产减少，主要原因是外汇影响和暂时性差异的变化。14. 14.Inventories 存货Inventories include batches of Joenja and RUCONEST and related work in progress. 库存包括多批次的Joenja和RUCONEST以及相关的在制品。Amounts in US$ ‘000 金额（千美元）June 30, 2026 2026年6月30日December 31, 2025 2025年12月31日Finished goods 成品16,406 16,40618,214 18,214Work in progress 进行中49,022 49,02246,688 46,688Balance at end of period 期末余额65,428 65,42864,902 64,902Changes in the adjustment to net realizable value: 可变现净值调整的变化：Amounts in US$ ‘000 金额（千美元）Period to June 30, 2026 截至2026年6月30日的期间Period to December 31, 2025 截至2025年12月31日的期间Balance at January 1 1月1日余额(13,060) (13,060)(8,663) (8,663)Addition to impairment 减值附加(6,195) (6,195)(6,193) (6,193)Release of impairment 减值转回206 206538 538Usage of impairment 减值的使用2,011 2,0112,522 2,522Currency translation 货币折算455 四百五十五(1,264) (1,264)Balance at end of period 期末余额(16,583) (16,583)(13,060) (13,060)The inventory valuation at June30, 2026, of US$65.4 million (December31, 2025: US$64.9 million) is stated net of an impairment of US$16.6 million (December31, 2025: US$13.1 million). The impairment relates to the write down of inventories to their net realizable value. 截至2026年6月30日，存货账面价值为6,540万美元（2025年12月31日：6,490万美元），已扣除1,660万美元的减值准备（2025年12月31日：1,310万美元）。该减值涉及将存货账面价值减记至其可变现净值。Inventories are available for use in commercial, preclinical and clinical activities. Estimates have been made with respect to the ultimate use or sale of product, taking into account current and expected sales as well as preclinical and clinical programs. These estimates are reflected in the additions to the impairment. 库存可用于商业、临床前和临床试验活动。已就产品的最终用途或销售作出估计，同时考虑了当前及预期的销售情况以及临床前和临床试验项目。这些估计反映在减值准备的增加中。The costs of materials used in research and development activities are presented under the research and development costs.. 研发活动中使用的材料成本列示于研发费用项下。The main portion of inventories at June30, 2026, have expiration dates starting beyond 2026 and are all expected to be sold and/or used before expiration. 截至2026年6月30日，库存的主要部分保质期均在2026年之后，且预计全部将在保质期内售出和/或使用完毕。Cash, cash equivalents and marketable securities 现金、现金等价物及有价证券Amounts in US$ ‘000 金额（千美元）June 30, 2026 2026年6月30日December 31, 2025 2025年12月31日Investments in money market funds 货币市场基金投资— —33,796 33,796Marketable securities 有价证券— —33,796 33,796Cash held at banks 存放于银行的现金60,007 六万零七145,305 145,305Investments in money market funds 货币市场基金投资98,274 九万八千二百七十四— —Cash and cash equivalents 现金及现金等价物158,281 158,281145,305 145,305Total liquidity 总流动性158,281 158,281179,101 179,101Since April 1, 2026, the marketable securities are considered to be cash equivalents as they are managed from that date as part of the Group’s total liquidity position and are held to meet potential short-term cash commitments rather than for investment purposes. The money market funds consist of LVNAV money market funds regulated under the EU Money Market Fund Regulation, which imposes liquidity, maturity, diversification and credit quality requirements broadly comparable to those applicable to SEC Rule 2a‑7 money market funds. 自2026年4月1日起，有价证券被视为现金等价物，因为从该日期起，它们作为集团整体流动性状况的一部分进行管理，并持有用于满足潜在的短期现金支付承诺，而非出于投资目的。货币市场基金包括根据欧盟《货币市场基金法规》受监管的LVNAV货币市场基金，该法规在流动性、期限、分散化和信用质量方面施加的要求，大致与美国证券交易委员会（SEC）第2a-7条规则适用的货币市场基金的要求相当。The carrying value includes accrued interest of US$0.3 million as of June30, 2026 (December31, 2025: US$0.1 million).. 截至2026年6月30日，账面价值包含应计利息30万美元（2025年12月31日：10万美元）。Cash is free at disposal of the Company. 现金可由公司自由支配。16. 16.Equity 股权The Company’s authorized share capital amounts to €10.56 million (US$12.0 million) and is divided into 1,056,000,000 ordinary shares with a nominal value of €0.01 each. All 707,781,240 shares outstanding at June30, 2026, have been fully paid-up. Other reserves include those reserves related to currency translation, share-based compensation expenses and other equity-settled transactions. 公司的法定股本为1,056万欧元（1,200万美元），分为1,056,000,000股普通股，每股面值0.01欧元。截至2026年6月30日，所有已发行的707,781,240股均已全额缴足。其他储备包括与外币折算、以股份为基础的薪酬费用以及其他以权益结算的交易相关的储备。. 。Please refer to the Condensed consolidated interim statement of changes in Equity. 请参阅简明合并中期权益变动表。The other reserves are made up as shown in the below table. 其他储备的构成如下表所示。Amounts in US$ ‘000 金额（千美元）Legal reserve Currency translation reserve (CTA) 法定准备金货币折算准备金（CTA）Legal Reserve Capitalized development cost 法定准备金资本化开发成本Reserve Convertible bond 可转换债券准备金Total 总计Balance at January 1, 2025 2025年1月1日余额(12,510) (12,510)76 七十六12,225 12,225(209) (209)Movement in the period 期间变动26,148 26,148(31) (31)— —26,117 26,117Balance at June 30, 2025 截至2025年6月30日的余额13,638 13,63845 四十五12,225 12,22525,908 25,908Balance at January 1, 2026 2026年1月1日余额14,941 14,94144 四十四13,835 13,83528,819 28,819Movement in the period 期间变动(8,057) (8,057)(44) （44）(377) (377)(8,477) (8,477)Balance at June 30, 2026 截至2026年6月30日的余额6,884 6,884— —13,458 13,45820,342 20,34217. 17.Convertible bonds 可转换债券In April 2024, the Company issued €100.0 million (US$113.9 million, based on the EUR/USD exchange rate as of June30, 2026) aggregate principal amount of 4.50% convertible bonds due 2029. 2024年4月，本公司发行了本金总额为1亿欧元（按截至2026年6月30日的欧元/美元汇率折算为1.139亿美元）的2029年到期的4.50%可转换债券。The movements of the convertible bonds were as follows: 可转换债券的变动情况如下：Amounts in US$ ‘000 金额（单位：千美元）Period to June 30, 2026 截至2026年6月30日的期间Period to December 31, 2025 截至2025年12月31日的期间Balance at January 1 1月1日余额98,055 98,05582,399 82,399Interest paid (cash flow) 支付的利息（现金流）(2,630) (2,630)(5,067) (5,067)Amortization 摊销4,230 4,2308,752 8,752Accrued interest 应计利息949 九百四十九933 九百三十三Currency translation 货币折算(2,734) (2,734)11,038 11,038Carrying value at end of period 期末账面价值97,870 97,87098,055 九万八千零五十五18. 18.Earnings per share and diluted shares 每股收益与稀释后股数Basic earnings per share is calculated based on the weighted average number of ordinary shares outstanding during the period. Diluted earnings per share in the case of a profit is computed based on the weighted average number of ordinary shares outstanding including the dilutive effect of shares to be issued in the future under certain arrangements such as option plans. 基本每股收益根据当期发行在外普通股的加权平均数计算。在盈利情况下，稀释每股收益根据包含期权计划等特定安排下未来将发行股份的稀释效应在内的发行在外普通股加权平均数计算。However, as the net result represents a loss, the diluted earnings per share are equal to the basic earnings per share. For 1H 2026 and 1H 2025, the basic and diluted earnings per share are:. 然而，由于净结果为亏损，稀释每股收益等于基本每股收益。2026年上半年和2025年上半年的基本每股收益和稀释每股收益分别为：1H 2026 2026年上半年1H 2025 2025年上半年Net profit (loss) attributable to equity owners of the parent (in US $ '000) 归属于母公司股东的净利润（亏损）（单位：千美元）(3,575) (3,575)(10,025) (10,025)Weighted average shares outstanding (in '000) 加权平均流通股数（单位：千股）705,383 705,383677,743 677,743Basic profit (loss) per share (in US$) 每股基本收益（亏损）（美元）(0.005) (0.005)(0.015) (0.015)Weighted average fully-diluted shares outstanding (in '000) 加权平均完全稀释后流通股股数（单位：千股）749,519 749,519744,282 744,282Fully-diluted profit per share (in US$) 完全稀释每股收益（美元）(0.005) (0.005)(0.015) (0.015)Diluted shares 稀释股The composition of the number of shares and share rights outstanding as well as authorized share capital as per June30, 2026 is provided in the table below: 截至2026年6月30日，已发行股份及股份权利数量以及授权股本的构成如下表所示：Amounts in '000 金额单位：千December 31, 2025 2025年12月31日Shares issued 已发行股份Other 其他June 30, 2026 2026年6月30日Issued shares 已发行股份701,680,440 七亿零一百六十八万零四百四十6,100,800 六百一十万零八百— —707,781,240 七亿零七百八十一万二千二百四十RSU 限制性股票单位19,853,668 一千九百八十五万三千六百六十八(726,337) (726,337)(2,185,735) (2,185,735)16,941,596 16,941,596Options 选项8,479,908 8,479,908(2,758,750) (2,758,750)(60,000) (60,000)5,661,158 5,661,158Convertible bonds 可转换债券81,492,951 八千一百四十九万二千九百五十一— —— —81,492,951 81,492,951LTIP 长期激励计划19,636,796 19,636,796(3,287,161) (3,287,161)3,818,129 3,818,12920,167,764 20,167,764Fully-diluted shares 完全稀释股数831,143,763 八亿三千一百一十四万三千七百六十三(671,448) (671,448)1,572,394 1,572,394832,044,709 八亿三千二百零四万四千七百零九Available for issue 可供发行224,856,237 二亿二千四百八十五万六千二百三十七671,448 671,448(1,572,394) (1,572,394)223,955,291 2亿2395万5291Authorized share capital 法定股本1,056,000,000 10.56亿— —— —1,056,000,000 10.56亿19. 19.Financial risk management and fair value 财务风险管理与公允价值Financial risk management 财务风险管理Pharming is exposed to several financial risks: market risks (being currency risk and interest rate risk), credit risks and liquidity risks. The Board of Directors and the Executive Committee are responsible for the management of currency, interest, credit and liquidity risks and as such ultimately responsible for decisions taken in this field. Pharming 面临多种财务风险：市场风险（包括汇率风险和利率风险）、信用风险以及流动性风险。董事会和执行委员会负责管理汇率、利率、信用和流动性风险，并因此对这些领域内作出的决策承担最终责任。The Group’s exposure to financial risks has not materially changed during the period.. 本集团在期间内面临的财务风险未发生重大变化。Fair value 公允价值The following table provides information on the fair value of financial instruments not measured at fair value as at the reporting date: 下表提供了在报告日未按公允价值计量的金融工具的公允价值信息：June 30, 2026 2026年6月30日December 31, 2025 2025年12月31日Carrying value 账面价值Fair value 公允价值Carrying value 账面价值Fair value 公允价值Liabilities: 负债：Convertible Bond (incl. equity component) 可转换债券（含权益部分）111,328 111,328145,807 145,807111,890 111,890157,481 157,481For financial instruments not included in the table above, the carrying amount is a reasonable approximation of fair value. 对于未包含在上述表格中的金融工具，其账面价值是公允价值的合理近似值。The following table presents information on the fair value measurement hierarchy of financial instruments measured at fair value: 下表列示了以公允价值计量的金融工具的公允价值计量层级信息：June 30, 2026 2026年6月30日December 31, 2025 2025年12月31日Level 1 一级Level 3 三级Total 总计Level 1 等级 1Level 3 3级Total 总计Items measured at fair value: 以公允价值计量的项目：Money market funds 货币市场基金98,274 98,274— —98,274 98,27433,796 33,796— —33,796 33,796Investments in debt instruments designated as at FVTPL 指定为以公允价值计量且其变动计入当期损益的债务工具投资— —6,520 6,5206,520 6,520— —6,703 6,7036,703 6,703Items for which fair value is disclosed: 披露公允价值的项目：Convertible Bond (incl. equity component) 可转换债券（含权益部分）145,807 145,807— —145,807 145,807157,481 157,481— —157,481 157,481Further information on the investments in debt instruments designated as at FVTPL is included in note 12. 有关指定为以公允价值计量且其变动计入当期损益的债务工具投资的进一步信息，请参阅附注12。During the six-month period ended June30, 2026, there have been no changes related to the fair value hierarchy. Comparative information was updated for consistency. 截至2026年6月30日的六个月期间，公允价值层级未发生任何变化。为保持一致性，已对比较信息进行了更新。20. Related party transactions 20. 关联方交易There are no material changes in the nature, scope, and scale in this reporting period compared to last year. More information is included in note 24 to the consolidated financial statements as at and for the year ended December31, 2025. 与去年相比，本报告期在性质、范围和规模方面均无重大变化。更多信息载于截至2025年12月31日止年度的合并财务报表附注24。21. Events since the end of the reporting period 21. 报告期结束后的事项There were no significant events since the end of the reporting period. 自报告期结束以来，未发生重大事项。Attachment 附件Pharming Group reports 2Q_1H26 results_EN_30JULY2026 Pharming Group 公布2026年第二季度及上半年业绩_EN_2026年7月30日

2026-06-16

·华溯同捷

转基因兔：精准基因修饰平台的物种优势与技术应用

引言 " 在生命科学与生物医药研究的实验动物谱系中，兔（Oryctolagus cuniculus）是最早服务于科学研究的物种之一。从发热与解热研究的经典模型到免疫血清制备的核心宿主，兔在生物医学中积累了超过百年的应用历史。然而，在转基因动物技术于20世纪80年代取得突破之后相当长的一段时间内，兔的基因组改造进展远落后于小鼠等啮齿类动物。由于兔缺乏可种系传递的多能干细胞系，体细胞核移植（SCNT）技术亦极为困难，基因靶向技术在兔中的发展长期受到严重制约。近年来的技术突破彻底改变了这一局面。锌指核酸酶（ZFN）、转录激活因子样效应物核酸酶（TALEN）以及CRISPR/Cas9等基因编辑核酸酶的问世，使得在兔中实现高效、精准的基因敲除和敲入成为可能。这些技术进步催生了大量基因组编辑兔模型的成功开发。与小鼠相比，基因组编辑兔模型在生理和生化方面更接近人类，因此在推动生物医学研究方面大有可为。事实上，早在1985年，首例转基因兔的诞生即被报道；此后，转基因兔品系被陆续建立并广泛应用于多种人类疾病的研究——尤其是心血管疾病领域。本文从物种比较优势、基因编辑技术的演进与标准化方法、心血管疾病模型的核心地位、免疫缺陷与人源化模型的突破、乳腺生物反应器的产业化应用、感染性疾病与眼科模型的前沿探索、标准化质量控制以及动物福利与3R原则等多个维度，系统阐述转基因兔作为精准基因修饰平台的科学基础与技术价值。 01 物种比较优势：为何选择兔作为转基因模型 HUASUTONGJIE 转基因动物模型的选择需在多个维度之间进行权衡：繁殖效率、遗传操作可行性、解剖与生理的人源相似性、器官大小以及实验操作的便利性。兔在多个关键维度上展现出独特的平衡优势。1.1 介于啮齿类与大型家畜之间的理想尺度兔的体型介于啮齿类与大型家畜之间——成年体重约2–5 kg——这一适中尺度使其在各种生理学操作中具有良好的适配性。与小鼠相比，兔的心脏更大、心率更慢（约130–250次/分对小鼠的500–600次/分），便于进行电生理记录和手术操作；与犬、猪等大型动物相比，兔的繁殖周期短（妊娠期29–36天）、性成熟早（4–6个月）、饲养成本低，可以在相对较短的时间内建立足够规模的转基因品系。1.2 脂质代谢与心血管系统的人源相似性兔在脂质代谢方面与人类具有独特的高度相似性。兔对膳食胆固醇极其敏感，饲喂高胆固醇饲料后可快速形成动脉粥样硬化病变。更重要的是，兔的载脂蛋白（apolipoprotein）谱和脂蛋白代谢模式与人类高度可比，而小鼠的脂蛋白以高密度脂蛋白（HDL）为主导，与人类的低密度脂蛋白（LDL）主导模式存在显著差异。兔的主要肌球蛋白重链（MHC）亚型为β-MHC，与人类一致，而啮齿类则以α-MHC为主。兔的心脏离子通道机制和复极化过程也与人类更为接近，使得兔成为研究长QT综合征等心脏离子通道疾病的理想模型——而大鼠和小鼠因复极化的离子机制与人类不同，被认为不适合用于此类研究。1.3 系统发育上的接近性在系统发育上，兔比啮齿类更接近人类。兔的解剖结构、循环生理功能与人类类似，在心血管研究中占据重要地位。这种进化上的接近性，使得人类疾病的致病基因在兔中表达时更可能引发与人类相似的病理改变，而小鼠中某些致病突变并不导致相应的病理变化。这一特性为转基因兔在转化医学中的独特价值提供了演化生物学层面的根本支撑。 02 基因编辑技术的演进与标准化方法 HUASUTONGJIE 2.1 从原核显微注射到精准基因编辑原核显微注射法是最早建立且至今仍广泛使用的转基因兔制作技术。其基本原理是在显微镜下将目的基因的DNA溶液直接注射到受精卵的雄原核中——注射成功的标志是雄原核体积膨大约为原来的1.5–2.0倍——然后将注射后的受精卵移植到受体母兔输卵管内“借腹怀胎”。该方法的优点是可靠性高、重复性好、目的基因的整合效率相对较高、导入基因片段的大小和类型不受限制，且转基因在世代之间可以稳定遗传。传统的原核显微注射法存在明显的局限性：对转基因的整合位点和拷贝数缺乏控制，导致表达水平不可预测，往往低于工业阈值。体细胞核移植（SCNT）技术为转基因兔的制作提供了另一条路径。其基本流程为：将外源基因转染到培养的兔体细胞中，挑选出转基因阳性细胞克隆，将其细胞核移植到成熟的去核兔卵母细胞中，构成转基因胚胎，再移植入代孕母兔体内。2007年，中国农科院北京畜牧兽医研究所成功培育出世界首例胎兔体细胞克隆荧光兔。SCNT技术的优势在于可以在细胞水平预先筛选转基因阳性克隆，确保所移植的胚胎均为转基因胚胎，从而大幅提高转基因动物的产出效率。然而，兔SCNT技术的效率长期偏低，制约了其在转基因兔大规模制备中的应用。基因编辑核酸酶时代的到来彻底改变了转基因兔的制备格局。ZFN、TALEN和CRISPR/Cas9等技术的出现，使得在兔中实现精准的基因敲除和敲入变得高效可行。其中，CRISPR/Cas9因其操作简便、效率高、成本低而成为目前兔基因组编辑中最广泛使用的工具。2.2 CRISPR/Cas9介导的兔基因组编辑标准化流程基于CRISPR/Cas9的兔基因组编辑已形成标准化的技术流程。核心步骤包括：靶点设计与sgRNA制备：根据目标基因序列设计特异性单链向导RNA（sgRNA），评估潜在的脱靶效应。基因编辑材料的制备与注射：将Cas9 mRNA（或Cas9蛋白）和sgRNA混合，通过显微注射技术注入兔受精卵的细胞质中。对于需要精确碱基替换的敲入实验，还需同时注射单链寡核苷酸供体模板作为同源重组修复的模板。为提高同源定向修复（HDR）效率，可添加HDR促进小分子如RS-1。胚胎移植与动物繁育：将注射后的受精卵移植到同步发情的受体母兔输卵管内。待仔兔出生后，通过PCR扩增和Sanger测序进行基因型鉴定。种系传递与纯合子培育：将获得的F0代基因编辑兔与野生型兔配种，产生F1代；同一突变系的F1代半同胞交配或回交繁殖F2代纯合子。研究表明，CRISPR/Cas9介导的基因编辑可在兔中实现种系传递。以PCSK9点突变兔的构建为例，研究者根据人兔同源性分析设计sgRNA和寡核苷酸供体模板，注射15只F0代兔中获得了1只纯合子和2只杂合子点突变兔，且突变可稳定遗传。这一案例充分展示了CRISPR/Cas9技术在兔精准基因修饰中的高效性。 03 心血管疾病模型：转基因兔的传统优势领域 HUASUTONGJIE 心血管疾病是全球发病率和死亡率的主要原因之一。转基因兔在这一领域的应用历史最为悠久、成果最为丰富——自首例转基因肝脂酶过表达兔诞生以来，转基因兔品系被陆续建立并用于多种心血管疾病的研究。3.1 动脉粥样硬化模型动脉粥样硬化的主要动物模型即为转基因兔。已有多种与脂质代谢相关的因子——包括人载脂蛋白A-I（apoA-I）、apoA-II、apoB-100、apoE2、apoE3、肝脂酶和脂蛋白脂酶等——在转基因兔中成功表达，为动脉粥样硬化的发病机制提供了新的认识。例如，人apoA-I的表达与主动脉粥样硬化程度的显著降低相关；而apoE2的表达则增加了对动脉粥样硬化的易感性。利用CRISPR/Cas9技术，研究者已成功构建了ApoE基因敲除兔，并对其肠道微生物群落特征进行了系统分析。LDLR和/或ApoE基因缺失的自发性高胆固醇血症兔模型也已建立。3.2 心肌病与心脏离子通道疾病与小鼠相比，兔的心脏电生理特性与人类更为接近，使转基因兔成为研究肥厚型心肌病和长QT综合征等心脏离子通道疾病的优越模型。这些疾病涉及的特异性基因突变在兔中可引发与人类相似的病理改变，而在小鼠中因心脏电生理的种属差异往往无法重现。转基因兔在心血管药物安全性评价——尤其是QT间期延长风险评估——中也具有重要的应用价值。 04 免疫缺陷与人源化模型：从基础免疫到抗体药物开发 HUASUTONGJIE 免疫系统相关疾病模型的构建是转基因兔研究的另一个核心方向。4.1 免疫缺陷兔模型的里程碑式突破 2013年，中国科学院广州生物医药与健康研究院研究团队利用TALEN技术对兔的重组激活基因（RAG）进行成功敲除，导致T细胞和B细胞发育阻滞，培育出了世界首例免疫缺陷性家兔模型。该模型为人类相关疾病（如Omenn综合征）的发病机制研究提供了关键的大动物平台。此后，针对不同免疫缺陷相关基因的敲除兔模型不断涌现。研究者针对PRKDC基因激酶功能区设计两条sgRNA进行大片段敲除，成功获得了具有免疫缺陷表型的PRKDC基因敲除兔。研究证明，PRKDC基因#78和#80外显子间大片段的敲除可有效破坏兔免疫系统，为再生医学、细胞治疗安全性测试、器官移植、癌症治疗和人类造血系统研究提供了良好的工具。此外，FOXN1基因敲除兔嵌合体的建立也为在普通环境下培育免疫缺陷兔奠定了基础。4.2 人源化抗体生产平台兔因其产生高效价、高亲和力抗体的独特能力，在抗体药物开发中具有天然的优势。通过将人免疫球蛋白基因座引入兔基因组，并敲除内源性兔免疫球蛋白基因，研究者已培育出首个用于人类抗体生产的转基因兔品系。这些转基因兔携带人源化免疫球蛋白位点，能够进行基因重排和基因转换，产生高特异性和高亲和力的人类抗体。我国在这一领域已取得重要进展。ATGC公司基于转基因兔的治疗性抗体开发平台（RbTx）正在建设中，兔免疫系统人源化改造工程已完成超过90%。利用人源化兔抗体平台可应急生产急性传染病抗体。这一平台有望显著加速抗体药物的开发速度并提供新的抗体品种选择。 05 乳腺生物反应器：从实验室到产业化 HUASUTONGJIE 转基因兔在生物医药领域最引人瞩目的产业化应用是乳腺生物反应器——利用乳腺特异表达的乳蛋白基因调控元件构建表达载体，通过基因导入技术制作转基因动物，指导外源基因在乳腺中特异性、高效表达，从乳汁中获得重组生物活性蛋白。5.1 兔作为乳腺生物反应器的独特优势兔作为乳腺生物反应器具有多方面的独特优势：兔可在屏障环境中作为无特定病原体（SPF）动物饲养，更符合药品生产质量管理规范（GMP）条件下生产药物的要求；迄今为止，尚未在兔中发现对人类致病的感染性病原体；兔具有培养周期短、安全性强、成本低等优势。兔乳腺生物反应器所生产的重组蛋白在结构上与人体内的天然蛋白非常接近，更加安全有效。5.2 FDA/EMA批准的转基因兔源药物目前，美国食品药品监督管理局（FDA）或欧洲药品管理局（EMA）批准上市的由动物乳腺生物反应器生产的重组蛋白质药物中，有两种来自转基因兔。重组C1酯酶抑制剂（商品名Ruconest®）于2010年获欧盟批准、2014年获美国FDA批准，用于治疗遗传性血管性水肿；重组活化人凝血因子VII（商品名Sevenfact®）于2020年获美国FDA批准。我国在这一领域也取得了突破性进展——成都生物制品研究所利用转基因兔乳腺生物反应器生产的重组人C1酯酶抑制剂，于2023年获得国家药品监督管理局药物临床试验批准通知书，成为国内首个利用转基因动物生产、获准进入临床研究的治疗性药物。5.3 新一代精准敲入技术驱动的产量提升传统的转基因兔乳腺生物反应器多采用原核显微注射法构建，存在整合位点和拷贝数不可控、重组蛋白产量低（通常为1–2 g/L或更低）等问题。2025年发表于Biological Research的研究报道了一项重要突破：研究者利用CRISPR/Cas9介导的敲入技术，将tdTomato报告基因精准插入到内源性β-酪蛋白基因（CSN2）位点——CSN2编码兔乳中含量最高的乳蛋白β-酪蛋白。纯合子敲入兔乳中的重组蛋白产量达到了15–20 g/L。这一策略展示了通过内源性高表达乳蛋白基因启动子驱动转基因表达的潜力，为动物制药领域的产量提升开辟了新的技术路径。 06 感染性疾病与眼科模型的前沿探索 HUASUTONGJIE 6.1 HIV/AIDS模型兔在HIV研究中的应用正成为一个新兴趋势，因为兔在分子水平上比啮齿类面临的病毒复制障碍更少。研究者已成功培育出表达人CD4（hCD4）基因的转基因兔。体外研究表明，来自hCD4转基因兔的外周血淋巴细胞在HIV-1感染后产生的p24核心蛋白量显著高于非转基因兔。进一步的转基因兔模型正在探索通过修饰兔CD4和CCR5受体来克服HIV-1进入兔细胞的第一道屏障。这些工作为建立首个可用于HIV-1感染研究的小型动物模型奠定了基础。6.2 视网膜退行性疾病模型兔的大眼睛使其在眼科研究中具有独特的优势。研究者已成功建立了多种转基因兔视网膜退行性疾病模型。例如，Tg P347L转基因兔模型被用于视网膜色素变性的研究。在两个高表达品系中，观察到了以视杆细胞为主的进行性视网膜退行性改变。这些模型为视网膜退行性疾病的病理生理学研究和新型治疗方法的开发提供了重要的大动物平台。 07 标准化质量控制与伦理考量 HUASUTONGJIE 7.1 微生物学等级与健康监测转基因兔作为实验动物的标准化质量控制，遵循GB 14922-2022《实验动物微生物、寄生虫学等级及监测》的规定，按照微生物控制程度分为普通级、清洁级、无特定病原体（SPF）级和无菌级等不同等级。对于乳腺生物反应器用途的转基因兔，SPF级饲养是基本要求，以确保重组蛋白药物不受外源病原体污染。转基因兔群体的健康状况需进行定期系统监测，检测范围覆盖多种病原体。7.2 遗传稳定性与种系传递验证转基因兔的遗传稳定性验证是确保模型可靠性的核心环节。需通过多代繁殖验证外源基因的种系传递能力。对于基因敲除兔，需通过PCR扩增、TA克隆、脱靶检测和Sanger测序等多重手段鉴定基因型。纯合子的获得通常需要通过F1代半同胞交配或回交方式实现。结语 " 转基因兔经过近四十年的发展——从1985年首例转基因兔的诞生到今天CRISPR/Cas9技术驱动下的精准基因修饰平台——已在心血管疾病模型、免疫缺陷模型、人源化抗体生产和乳腺生物反应器等多个领域确立了不可替代的地位。2024年发表于Zoological Research的综述系统总结了可用于基因组编辑兔的新型基因编辑方法及其在生物医学中的应用和前景，强调了它们在转化医学中的特殊影响和未来潜力。展望未来，转基因兔的发展面临若干重要方向。在精准基因修饰方面，CRISPR/Cas9技术的持续优化——包括提高同源重组修复效率、减少脱靶效应以及实现多基因同时编辑——将使转基因兔模型的构建更加高效和精准。多基因疾病模型的设计——如同时携带人类T2DM易感基因和IAPP高表达基因的“串联”突变兔——将使模型更为完整地模拟人类复杂疾病。在人源化模型方面，兔免疫系统人源化改造工程的持续推进有望使转基因兔成为治疗性抗体发现的常规平台。人源化兔抗体平台的产品管线正在拓展中。在产业化应用方面，基于内源性高表达乳蛋白基因启动子的精准敲入策略有望将乳腺生物反应器的重组蛋白产量提升至工业可行水平，推动更多转基因兔源药物进入临床和上市。在标准化建设方面，尽管转基因兔在心血管、免疫缺陷和眼科等经典研究领域积累了丰富的应用数据，但与小鼠等成熟模型相比，转基因兔的全国统一遗传管理标准和跨实验室数据共享机制仍有待完善。不同实验室之间在基因编辑策略、品系背景和表型评估方法上的差异，是制约转基因兔模型数据可比性的主要瓶颈。必须强调的是，转基因兔并非对所有生物医学问题都成立的最佳模型——小鼠在基因功能的基础研究和快速筛选中的优势仍然不可替代，大型家畜在异种器官移植等领域的体型匹配性更为优越。然而，当研究问题涉及心血管系统的电生理特性、脂质代谢的网络调控、大分子药物的乳腺表达与纯化，或者需要在与人类心脏离子通道机制可比的大动物中验证基因功能时，转基因兔凭借其介于啮齿类与大型家畜之间的理想尺度、与人类高度相似的脂质代谢和心脏电生理特征，以及经过数十年验证的技术可操作性和产业化可行性，仍然是当前转化医学研究中最具成本效益和预测价值的精准基因修饰平台之一。参考文献 [1] 韩杨, 周佳乐, 张仁泉, 等. 基因编辑兔：有潜力成为研究多种疾病的实验动物模型[J]. 动物学研究, 2024, 45(2): 253-262. [2] Peng X. Transgenic rabbit models for studying human cardiovascular diseases[J]. Comparative Medicine, 2012, 62(6): 472-479. [3] Yang D, et al. Generation of Rabbit Models by Gene Editing Nucleases[J]. Methods in Molecular Biology, 2019. [4] Development of a high-yield Rabbit line for enhanced animal pharming[J]. Biological Research, 2025, 58: 73. [5] Construction of PCSK9 point mutation rabbits using CRISPR/Cas9[J]. 浙江大学学报(医学版), 2021, 50(2): 229-238. [6] 转基因兔乳腺生物反应器的研究进展[EB/OL]. 2024年科普报告. [7] 夜光兔[EB/OL]. 百度百科. [8] 转基因家兔模型制作方法[J]. [9] 转基因兔的制作[J]. 实验动物管理与实用技术手册, 2015. [10] 利用CRISPR/Cas9技术构建PRKDC基因敲除的免疫缺陷兔[J]. 2023. [11] 广州生物院用TALENs基因敲除技术成功培育免疫缺陷性家兔[EB/OL]. 中国科学院, 2013. [12] Rabbits transgenic for human IgG genes recapitulating rabbit B-cell biology to generate human antibodies[J]. [13] 基因修饰兔的发展及其在人类疾病研究中的应用[J]. 2023. [14] GB 14922-2022 实验动物微生物、寄生虫学等级及监测[S]. 2022. [15] Russell WMS, Burch RL. The Principles of Humane Experimental Technique[M]. London: Methuen, 1959. 小鼠手术前后处理常规

100 项与 Conestat alfa 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10845	Conestat alfa	B06AC04	DB09228

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
遗传性血管性水肿	欧盟	Pharming Group NV	2010-10-28
遗传性血管性水肿	冰岛	Pharming Group NV	2010-10-28
遗传性血管性水肿	列支敦士登	Pharming Group NV	2010-10-28
遗传性血管性水肿	挪威	Pharming Group NV	2010-10-28

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性缺血性卒中	临床2期	瑞士	Pharming Technologies BV	2022-03-16
不稳定型心绞痛	临床2期	瑞士	Pharming Technologies BV	2021-04-21
非ST段抬高型心肌梗死	临床2期	瑞士	Pharming Technologies BV	2021-04-21
新型冠状病毒感染	临床2期	巴西	Pharming Technologies BV	2020-08-06
新型冠状病毒感染	临床2期	墨西哥	Pharming Technologies BV	2020-08-06
新型冠状病毒感染	临床2期	瑞士	Pharming Technologies BV	2020-08-06
急性肾损伤	临床2期	瑞士	Pharming Technologies BV	2017-01-01
抗体介导的排斥反应	临床2期	美国	Pharming Technologies BV	2010-12-01
器官移植排斥	临床2期	美国	Pharming Technologies BV	2010-12-01

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临床结果

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分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01188564 \| NCT00262301 \| NCT00225147 (Pubmed \| Adv Ther)	临床3期	遗传性血管性水肿	108	rhC1-INH 50 U/kg	觸觸顧壓鏇選淵網餘醖(築蓋構襯廠憲觸壓製鹽) = 醖繭鑰夢鹽窪膚顧鏇膚築壓窪鹹鹹鬱襯衊鹹憲 (膚鏇構選廠齋選醖簾壓, 0.55 ~ 1.50) 更多	积极	2026-05-20
				Placebo	觸觸顧壓鏇選淵網餘醖(築蓋構襯廠憲觸壓製鹽) = 夢繭選範淵夢襯鹽獵簾築壓窪鹹鹹鬱襯衊鹹憲 (膚鏇構選廠齋選醖簾壓, 3.00 ~ 8.05) 更多
NCT01359969 (CTgov)	临床2期	遗传性血管性水肿	57	rhC1INH	築蓋網獵遞網衊鹽簾選(鬱淵選醖餘壓艱艱築繭) = 鑰鏇範遞簾襯構網繭壓鏇鑰簾構繭築遞觸艱夢 (憲膚壓膚鏇鏇壓壓糧衊, 製餘糧憲齋膚築鬱遞鏇 ~ 餘膚願襯鏇簾壓鬱鏇憲) 更多	-	2024-03-29
NCT04530136 (CTgov)	临床2期	新型冠状病毒感染	38	Ruconest (Ruconest)	遞糧鑰窪獵憲積鏇襯選 = 構餘蓋築糧窪簾願鹽願廠選壓鏇鬱憲鏇築簾蓋 (積遞艱艱構艱願衊夢壓, 築顧鏇觸製顧艱窪蓋淵 ~ 顧醖餘壓鏇衊構鹹膚艱) 更多	-	2024-02-16
				Ruconest (Standard of Care)	遞糧鑰窪獵憲積鏇襯選 = 鏇繭網襯繭糧範衊淵遞廠選壓鏇鬱憲鏇築簾蓋 (積遞艱艱構艱願衊夢壓, 衊顧鏇蓋鏇鬱壓願顧鹹 ~ 鬱膚膚壓願蓋蓋窪願積) 更多
NCT02869347 (PROTECT, ERA2019)	临床2期	肾脏疾病 urinary neutrophil gelatinase-associated lipocalin (NGAL) \| serum C1 inhibitor levels \| cystatin C	77	Conestat alfa	選網壓簾夢獵積網顧襯(顧繭簾廠鹽繭鬱鏇齋膚) = 糧繭蓋鏇膚壓遞膚獵鑰遞鬱憲鑰顧鏇壓壓網衊 (餘鹽醖膚構網簾築淵艱 ) 更多	积极	2019-06-13
				Placebo	選網壓簾夢獵積網顧襯(顧繭簾廠鹽繭鬱鏇齋膚) = 壓觸鹹構選醖衊襯鹽簾遞鬱憲鑰顧鏇壓壓網衊 (餘鹽醖膚構網簾築淵艱 ) 更多
NCT02247739 (CTgov)	临床2期	遗传性血管性水肿	32	Recombinant human C1 inhibitor (rhC1INH Twice Weekly)	鑰鬱鹽範憲簾選簾艱糧(簾餘蓋鏇廠範構鏇窪製) = 願網鬱顧齋醖繭顧遞觸衊鹹襯製範積淵顧餘簾 (觸顧獵鑰衊鏇窪獵艱糧, 衊淵製鹹鏇遞蓋獵簾願 ~ 膚鬱獵製窪鹹醖鬱蓋築) 更多	-	2017-12-08
				Recombinant human C1 inhibitor (rhC1INH Once Weekly)	鑰鬱鹽範憲簾選簾艱糧(簾餘蓋鏇廠範構鏇窪製) = 衊衊膚選範憲鹹鑰夢憲衊鹹襯製範積淵顧餘簾 (觸顧獵鑰衊鏇窪獵艱糧, 醖範鬱膚選獵蓋繭鹹衊 ~ 鹽窪糧憲憲顧衊窪鹽襯) 更多
NCT01188564 (CTgov)	临床3期	遗传性血管性水肿	75	rhC1INH (rhC1INH)	鑰繭憲簾醖醖網願獵憲(齋蓋夢網繭鹽壓淵鏇齋) = 襯範壓壓鑰願鑰鬱積蓋範蓋憲築膚網鑰醖遞範 (蓋繭範觸壓遞願鏇餘廠, 衊觸鑰憲廠鹹繭壓衊鬱 ~ 製鑰範鬱選製積繭顧夢) 更多	-	2015-08-07
				Placebo (Saline) (Placebo (Saline))	鑰繭憲簾醖醖網願獵憲(齋蓋夢網繭鹽壓淵鏇齋) = 獵遞鑰願鑰獵窪鹹簾鑰範蓋憲築膚網鑰醖遞範 (蓋繭範觸壓遞願鏇餘廠, 獵願廠鹽襯醖積鹹鬱鬱 ~ 顧壓願網積膚觸繭餘憲) 更多
NCT01188564 (Pubmed \| Ann Allergy Asthma Immunol) 人工标引	临床3期	遗传性血管性水肿	75	rhC1INH	簾遞鹹鬱獵選鬱鹹鹹鏇(簾觸鏇繭鑰淵積鑰艱鬱) = 鬱衊餘齋範齋壓製醖願範膚糧艱鹹艱襯淵憲壓 (艱顧範艱選夢廠鬱鹽膚, 61 ~ 150) 更多	积极	2014-02-01
				Placebo	簾遞鹹鬱獵選鬱鹹鹹鏇(簾觸鏇繭鑰淵積鑰艱鬱) = 襯繭製網構壓蓋齋簾窪範膚糧艱鹹艱襯淵憲壓 (艱顧範艱選夢廠鬱鹽膚, 93 ~ NE) 更多
NCT00851409 (OPERA, CTgov)	临床2期	遗传性血管性水肿	25	Recombinant Human C1 Inhibitor	鹹積膚鹽蓋鏇製網遞醖(醖糧範糧鏇網鏇壓蓋繭) = 糧鹹襯構淵願願壓艱願廠憲夢築願選獵選遞壓 (簾廠網膚製築糧繭壓鹽, 範窪繭繭糧鹽網鹹觸膚 ~ 窪廠憲積艱鑰鹽鬱憲襯) 更多	-	2013-01-31
NCT00262301 (CTgov)	临床3期	遗传性血管性水肿	75	recombinant human C1 inhibitor (100 IU/kg "rhC1INH")	窪構襯鬱齋網遞糧淵淵(積願構顧繭鬱齋願鬱廠) = 淵鬱糧憲構鑰選繭構範積繭壓壓糧選鹹鬱醖積 (餘夢壓壓網憲鏇顧襯壓, 憲願衊淵願選遞衊鏇糧 ~ 願襯築淵網網顧製艱襯) 更多	-	2012-08-30
				Placebo (Saline)	窪構襯鬱齋網遞糧淵淵(積願構顧繭鬱齋願鬱廠) = 獵鑰壓鹹鑰醖醖鬱構衊積繭壓壓糧選鹹鬱醖積 (餘夢壓壓網憲鏇顧襯壓, 襯獵蓋餘醖鏇選繭範糧 ~ 範鹽鏇艱鬱蓋憲齋鬱襯) 更多