Pharming presents positive Phase II topline data for leniolisib in genetic PIDs with immune dysregulation at ESID 2026

All 12 participants who completed the study enrolled in a three-year extension to continue receiving treatment.

Rhea-AI Summary

Pharming (PHAR) presented Phase II topline data for leniolisib showing improvements in genetically identifiable primary immunodeficiencies with immune dysregulation beyond APDS.

The single-arm, open-label study enrolled 13 participants treated twice daily over 20 weeks. Mean spleen volume fell 26.4% from baseline in 11 evaluable participants; lymph-node index lesion size fell 33.7% in four. Lung gas-exchange capacity increased by a mean of 8.0% among seven participants impaired at baseline. Lung disease scores decreased in four of five evaluable participants; liver stiffness improved in two of three with elevated baseline stiffness.

All treatment-related adverse events were Grade 1, with no new safety signals. Two participants had serious events deemed unrelated to leniolisib; one discontinued due to acute hepatitis. All 12 completers entered a three-year extension. Pharming expects separate CVID trial topline results in November.

Positive

• Minor pointSpleen volume decreased 26.4% on average from baseline; 10 of 11 evaluable participants showed reductions.
• Minor pointLymph-node index lesion size decreased 33.7% on average from baseline in all four evaluable participants.
• Minor pointLung gas-exchange capacity increased by a mean of 8.0% in seven participants with baseline impairment.
• Minor pointCT-assessed lung disease scores decreased in four of five evaluable participants.
• Minor pointLiver stiffness improved in two of three participants with heightened baseline stiffness.

3 minor points

• Minor pointTreatment-related adverse events were all Grade 1; no new safety signals were identified.
• Minor pointAll 12 study completers enrolled in the three-year extension study.
• Minor point. Forward-looking: it has not happened yet and may not happen.Separate CVID trial topline results are expected in November to inform potential registrational study plans.

Negative

• Minor pointSingle-arm, open-label design provided no control group in the 13-participant, 20-week study.
• Minor pointInfections were the most common adverse events observed.
• Minor pointTwo participants experienced serious adverse events deemed unrelated to leniolisib.
• Minor pointOne participant with a history of portal hypertension discontinued treatment early due to acute hepatitis.

News Explained

The estimated populations are broader than APDS alone, but remain potential populations rather than established treatment groups.

For the additional, still-investigational uses, Pharming estimates about 7.5 patients per million for genetic PIDs and about 39 per million for CVID, versus about 1.5 per million for APDS; the first two populations overlap.

Pharming says leniolisib’s safety and efficacy have not been established for these uses, so the estimates do not represent approved treatment populations.

Key Figures

Study participants: 13 participants Mean spleen-volume reduction: 26.4% (n=11) Mean index-lesion size reduction: 33.7% (n=4) +5 more

Study participants

13 participants

Phase II study in genetically identifiable PIDs with immune dysregulation

Mean spleen-volume reduction

26.4% (n=11)

From baseline; reductions in 10 of 11 evaluable participants

Mean index-lesion size reduction

33.7% (n=4)

Lymph nodes; reductions in all four evaluable participants

Mean DLCO increase

8.0% (n=7)

Participants with impaired gas exchange at baseline

Interstitial lung disease score decrease

4 of 5 participants

CT-assessed scores among evaluable participants

Liver stiffness improvement

2 of 3 participants

Participants with heightened stiffness at baseline

Treatment-related adverse events

Grade 1

All treatment-related adverse events

Study completers entering extension

12 participants

All participants who completed the study enrolled in the three-year extension

Previous Clinical trial Reports

1 past event · Latest: Sep 22

Same Type 1 event

1. Sep 22

   Phase II topline data

   24h Move

   +4.2%

   Reported the same Phase II cohort and mean 26.4% spleen-volume reduction ahead of the conference presentation.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

pi3kδ inhibition, open-label, intra-patient dose-escalation, cvid, +1 more

5 terms

pi3kδ inhibition medical

"supporting the potential of targeted PI3Kδ inhibition"

pi3kδ inhibition is the pharmacological blocking of the delta (δ) isoform of phosphoinositide 3-kinase (PI3K), an enzyme that creates signaling lipids (like PIP3) that activate cell-growth and survival pathways. Because the delta isoform is concentrated in white blood cells, inhibitors reduce activation, proliferation and survival signals in immune cells (notably B and T cells), which is the intended mechanism in treating certain blood cancers and immune disorders; selectivity for the δ isoform matters because other PI3K isoforms control metabolism and different tissues, and δ inhibition commonly carries effects such as reduced immune function and related safety considerations.

open-label technical

"a single-arm, open-label, intra-patient dose-escalation Phase II study"

Open-label describes a situation where everyone involved in a study or process knows the full details, such as who is receiving a treatment or intervention. For investors, understanding whether a project or product is open-label helps gauge the level of transparency and potential biases, influencing trust and decision-making. It’s like knowing whether a test or experiment is conducted openly or behind closed doors.

intra-patient dose-escalation technical

"a single-arm, open-label, intra-patient dose-escalation Phase II study"

A trial design in which a single participant receives increasing doses of the investigational drug over time rather than remaining at the initial dose or being compared only across different patients; dose is raised for that same patient after predefined safety and tolerability criteria are met. This approach is used in early-phase studies to gather individual tolerability and pharmacologic information, and it changes how safety and response are attributed because adverse events and drug levels must be interpreted across sequential dose exposures in the same person rather than between different subjects.

cvid medical

"Nine of the 13 participants also had a diagnosis of common variable immunodeficiency (CVID)."

Common Variable Immunodeficiency (CVID) is a lifelong immune system disorder in which the body fails to produce enough protective antibodies, leaving people prone to frequent and sometimes severe infections. Investors pay attention because therapies, diagnostics, and long‑term care for CVID can drive sales and clinical trial activity; successful treatments or regulatory approvals can materially affect companies developing immune‑related drugs, much like fixing a leaky roof reduces ongoing repair costs for a homeowner.

dlco medical

"the percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO)"

DLCO is a medical test that measures how well gases move from the air in the lungs into the blood by using a small amount of carbon monoxide as a tracer; it quantifies the lung’s ability to transfer oxygen to the bloodstream. For investors, DLCO values are important because they help show whether respiratory drugs, devices or treatments improve or harm lung function—like testing how quickly water soaks through a sponge to judge its condition—which can affect clinical trial outcomes, regulatory decisions and market potential.

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• 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 www.pharming.com 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. 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.

Attachment

• Pharming presents Phase II topline data leniolisib PIDs_EN_14OCT2026

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Pharming's Phase II leniolisib trial show beyond APDS?

The trial showed reductions in spleen volume and lymph-node lesion size, alongside improvements in lung and liver measures. Mean spleen volume decreased 26.4% from baseline in 11 evaluable participants, and mean lymph-node index lesion size decreased 33.7% in four. The study was single-arm and open-label.

What dosing schedule did Pharming use in the Phase II leniolisib PID trial?

Participants received leniolisib twice daily for 20 weeks, with doses increasing within each participant. Treatment began at 10 mg for four weeks, increased to 30 mg for four weeks, and then increased to 70 mg for 12 weeks.

Which genetic conditions were included in Pharming's Phase II leniolisib PID trial?

The trial enrolled participants with genetically identifiable primary immunodeficiencies driven by variants in CTLA4, SOCS1, NFKB1 or FAS. Nine of the 13 participants also had common variable immunodeficiency, or CVID.