Leniolisib phosphate

First clinical data for leniolisib in a larger group of PID participants beyond APDS, supporting the potential of targeted PI3Kδ inhibition to address immune dysregulation Leniolisib was well-tolerated, with benefits observed across multiple measures of immune dysregulation, including improvement in lymphoproliferation and positive trends in lung and liver disease markers All participants who completed the study elected to continue receiving treatment in a long-term extension study Leiden, the Netherlands, October 14, 2026: Pharming (Euronext Amsterdam: PHARM/Nasdaq: PHAR), a global biotechnology company focused on rare immune and genetic diseases, today presented positive topline data from its Phase II trial of leniolisib in genetically identifiable primary immunodeficiencies (PIDs) with immune dysregulation linked to altered PI3Kδ signaling. The data, accepted as a late-breaking abstract, were presented as a poster at the 22nd Biennial Meeting of the European Society for Immunodeficiencies (ESID), taking place October 14-17, 2026, in Maastricht, the Netherlands. “These data provide the first clinical evidence that leniolisib can produce improvements across multiple manifestations of immune dysregulation in conditions beyond APDS, with encouraging signals in lymphoproliferation, pulmonary function, and liver disease,” said Anurag Relan, Chief Medical Officer of Pharming. “The consistent reductions in spleen volume in nearly all evaluable participants are particularly encouraging. Splenomegaly is a measurable sign of lymphoproliferation, and these reductions suggest leniolisib is acting on a core driver of the disease process. The trends in pulmonary findings are also particularly noteworthy, as even small improvements in progressive lung disease were not expected over such a short treatment period.” This trial is a single-arm, open-label, intra-patient dose-escalation Phase II study that enrolled 13 participants with genetically identifiable PIDs driven by variants in the CTLA4 , SOCS1 , NFKB1 or FAS genes. Nine of the 13 participants also had a diagnosis of common variable immunodeficiency (CVID). Participants received leniolisib twice daily for 20 weeks, escalating from 10 mg (4 weeks) to 30 mg (4 weeks) to 70 mg (12 weeks). Key results include: Safety: Leniolisib was generally well-tolerated across all 4 genotypes associated with dysregulated PI3Kδ signaling. Safety findings were consistent with the known disease profile, with infections as the most common adverse events (AEs) observed, and no new safety signals identified. All treatment-related AEs were Grade 1. Two study participants experienced serious AEs that were deemed unrelated to leniolisib. One participant, with a history of portal hypertension, discontinued treatment early due to acute hepatitis. Spleen volume: Mean reduction from baseline of 26.4% (n=11), with reductions observed in 10 of 11 evaluable participants. Lymph nodes: Mean reduction from baseline of 33.7% in index lesion size (n=4), with reductions observed in all four evaluable participants. Pulmonary function: Among participants with impaired gas exchange at baseline (n=7), the percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO) increased by a mean of 8.0%. Consistent with this, CT-assessed interstitial lung disease scores also decreased in 4 of 5 evaluable participants. Liver: Improvement in liver stiffness in 2 of 3 participants with heightened stiffness at baseline. All 12 participants who completed the study enrolled in the three-year extension study ( NCT06990529 ). Added Dr. Relan: “Together, these results reinforce our broader strategy of evaluating PI3Kδ inhibition across PIDs characterized by immune dysregulation, regardless of genetic cause. We look forward to reporting topline results from our separate Phase II trial in CVID, expected in November, which will inform our plans for a potential registrational study in the broader CVID population.” Based on estimated prevalence rates, these genetically identifiable PIDs and CVID with immune dysregulation represent a broader potential patient population than APDS, with estimated prevalence of approximately 7.5 patients per million for genetic PIDs and approximately 39 patients per million for CVID, including overlap between the genetic PID and CVID populations, compared with approximately 1.5 patients per million for APDS. About leniolisib Leniolisib is an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor designed to address PI3Kδ-driven immune dysregulation across primary immunodeficiencies (PIDs). Leniolisib, marketed under the brand name Joenja®, is approved and commercially available in multiple countries for the treatment of activated phosphoinositide 3-kinase delta syndrome (APDS) an ultra-rare and progressive PID characterized by immune dysregulation and deficiency. Beyond APDS, leniolisib is being evaluated in clinical trials for additional PIDs characterized by PI3Kδ-driven immune dysregulation, including common variable immunodeficiency (CVID). These PIDs share many of the same clinical manifestations, including lymphoproliferation, autoimmunity, gastrointestinal disease, and lung disease. The safety and efficacy of leniolisib have not been established for these investigational uses. About Pharming Pharming Group N.V. (Euronext Amsterdam: PHARM/Nasdaq: PHAR) is a global biotechnology company that develops and commercializes innovative medicines for people living with rare immune and genetic diseases. We combine specialized scientific, medical, regulatory and commercial expertise to advance a focused portfolio of approved medicines and development programs that address significant unmet medical needs. Guided by insights from patients and the wider rare disease community, we are dedicated to delivering innovative therapies for some of the most challenging rare diseases. Pharming is headquartered in Leiden, the Netherlands, with operations in the United States and Europe. For more information, visit and find us on LinkedIn . For further public information, contact: Pharming Michael Levitan, VP Investor Relations & 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: mailto: 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 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. 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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. Attachment Pharming presents Phase II topline data leniolisib PIDs_EN_14OCT2026

iOnctura’s PI3K delta inhibitor shows promise in phase 1 study in patients with mostly pre-treated metastatic melanoma. In a head-to-head comparison of patient tumors, iOnctura’s roginolisib outperformed Gilead’s Zydelig (idelalisib) in reducing cancer signaling pathway effectors. The two-part phase 1 study examined the safety and efficacy of roginolisib in 44 patients with advanced solid and hematologic malignancies. Part A was a dose-escalation study done in 24 patients, while part B was a dose expansion for roginolisib as a second-line treatment in 20 patients with metastatic uveal melanoma. In the 44 patients that were dosed with roginolisib, the median overall survival (mOS) was 20.8 months . Although there was no placebo head-to-head comparison in this trial, historically, patients receiving immunotherapies as a second-line treatment have an mOS of seven months . The drug was safe with no dose-limiting toxicities or dose modifications, and grade 3 adverse events were observed in three of the 44 patients. Roginolisib also demonstrated a predictable pharmacokinetic profile, decreased T regulatory cell abundance and increased activated CD8+ T cells. “Patients are progressing very rapidly, even on treatment, and then there is nothing for patients after they've progressed. This is where we believe roginolisib fits perfectly,” iOnctura CEO Catherine Pickering, Ph.D., told Fierce. “We're not adding toxicity. We're not adding [a] burden to patients, but we're extending life—and that's really important for us as a company.” The PI3K signaling pathway is one of the most frequently dysregulated pathways across multiple cancer types, including uveal melanoma. Cancer cells receive an extracellular signal that binds to its receptor to trigger the PI3K cascade, which includes production of a second messenger called PIP3, which subsequently leads to downstream activation of cancer signaling pathways. Uveal melanoma is a rare cancer of the back of the eye and spreads to other organs such as the liver. “As a company, we are really interested in pursuing solid tumor indications, and therefore we selected an indication where we knew that immunosuppression was a driver of the malignancy,” Giusy Di Conza, Ph.D., head of research and translational science at iOnctura, told Fierce. “By relieving immunosuppression, you could reawaken the immune system to fight the tumor.” iOnctura spun out of a pact with Merck KGaA and Cancer Research UK in 2017. Both founding organizations contributed assets designed to modulate immunosuppressive mechanisms that affect the tumor microenvironment, one being Merck KGaA’s roginolisib, which was at the time developed as a lupus drug. Roginolisib is an oral “conformation stabilizer of the inactive form of PI3K delta” designed to revert immunosuppression and inhibit cancer cell growth and proliferation, Pickering explained. It binds into a unique site in the inactive state of PI3K delta and causes a conformational shift, preventing ATP from binding and fueling the enzyme, while also preventing a shift to the activated state. Alongside the phase 1 trial results, iOnctura also published a paper describing the binding mechanism of roginolisib and comparing its efficacy to Gilead’s idelalisib, also a PI3K delta inhibitor. The researchers found that roginolisib was associated with more sustained suppression of PIP3 formation in tumor samples from patients with chronic lymphocytic leukemia. Besides idelalisib, there are a handful of other FDA-approved PI3K-targeting drugs. Secura Bio’s duvelisib is a dual PI3K delta and gamma inhibitor approved for B-cell blood cancers, while Pharming Group’s Novartis-licensed selective PI3K delta inhibitor Joenja is approved for a rare genetic immune disorder. PI3K alpha inhibitors such as Novartis’ Piqray and Roche’s Itovebi are approved in breast cancer. But there are no PI3K delta inhibitors approved for solid tumor indications, which is why iOnctura is pursuing this target in solid tumors, Pickering noted.