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The multinational phase III study is evaluating leniolisib tablets in children 4 to 11 years of age with APDS, a rare primary immunodeficiency.

LEIDEN, The Netherlands, Feb. 21, 2023 /PRNewswire/ -- Pharming Group N.V. ("Pharming" or "the Company") (EURONEXT Amsterdam: PHARM)/(Nasdaq: PHAR) announces that it has enrolled the first patient in its Phase III clinical trial (NCT05438407) evaluating the investigational drug leniolisib, an inhibitor selective oral phosphoinositide 3-kinase delta (PI3Kδ) in children with activated phosphoinositide 3-kinase delta syndrome (APDS). There is currently no approved treatment for this complex and progressive disease caused by genetic variants.

At centers in the United States, Europe, and Japan, the single-arm, open-label, multinational clinical trial will evaluate the safety, tolerability, and efficacy of leniolisib in approximately 15 children 4 to 11 years of age with a confirmed diagnosis of APDS. The primary efficacy endpoints of the study are reduction in index lymph node size and increase in the ratio of naïve B cells to total B cells from baseline at 12 weeks. Secondary endpoints include an assessment of the ability of leniolisib to modify health-related quality of life based on measures of physical, social, emotional, and school functioning using a validated patient questionnaire.

Pharming plans to initiate a similar clinical trial in the third quarter of 2023 that will include children 1 to 6 years of age, with APDS, to evaluate a new pediatric formulation of leniolisib. Eligible patients enrolled in any of the pediatric trials will continue to receive leniolisib for one year after the initial 12-week treatment period via an open-label extension trial.

Manish Butte, MD, PhD, E. Richard Stiehm Endowed Chair, Senior Lecturer in the Department of Pediatrics and Chief of the UCLA Division of Immunology, Allergy, and Rheumatology, commented:

"In the treatment of APDS, the current standard is to use a range of supportive therapies. Although these therapies can treat some of the manifestations of APDS, they do not address the underlying cause of the disease. Pharming's studies of leniolisib in children with APDS are important to assess for the possibility of minimizing symptoms earlier in the progression of the disease."

Pharming's program for the clinical development of leniolisib in pediatric APDS is supported by positive data from a phase II/III clinical trial that investigated the drug as a treatment for patients with the disease 12 years and older. As announced on February 2, 2022, and recently detailed in Blood1, the international medical journal of the American Society of Hematology, the trial met its two co-primary endpoints, with patients taking leniolisib versus placebo achieving significant reductions in lymphoproliferation, as measured by index lymph node size, and increases in immunophenotype corrections, as measured by the percentage of naïve B cells in peripheral blood.

During the first half of 2022, positive opinions were received from the European Medicines Agency (EMA) and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) on the Pediatric Investigation Plan (PIP) of leniolisib as a treatment for APDS in children. The PIPs included the plans for both pediatric clinical trials.

Anurag Relan, MD, MPH, Pharming's chief medical officer, commented:

"I am pleased that we have initiated the first trial in our Phase III pediatric clinical program evaluating leniolisib in children with APDS, and I am looking forward to our second pediatric trial getting underway. Building on the encouraging results of our successful study of In phase II/III patients 12 years and older with APDS, we are committed to bringing leniolisib to even younger patients with the goal of intervening before they develop immune-related symptoms that are likely to progress throughout their lives. Focusing on APDS patients of all ages, we are dedicated to collaborating with regulatory authorities to generate regulatory requests for approval that could support the treatment of children under 12 years of age living with this disease. "

Based on the results of the Phase II/III trial and the data from the long-term open-label extension, the US Food and Drug Administration (FDA) is conducting a priority review of the new drug application. Pharming for leniolisib as a treatment for adolescents and adults with APDS and has assigned a Prescription Drug User Fee Act (PDUFA) target date of March 29, 2023. In addition, Pharming's Marketing Authorization Application (MAA) for leniolisib in the same patient population is being evaluated by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). Pharming expects the CHMP to issue its opinion on the leniolisib marketing authorization application in the second half of 2023.

About Activated Phosphoinositide 3-Kinase δ Syndrome (APDS)

APDS is a rare primary immunodeficiency that affects approximately 1 to 2 people per million. APDS is caused by variants in either of two genes, PIK3CD or PIK3R1, that regulate white blood cell maturation. Variants of these genes lead to hyperactivity of the PI3Kδ (phosphoinositide 3-kinase delta) pathway.2,3 Balanced signaling in the PI3Kδ pathway is essential for physiological immune function. When this pathway is overactive, immune cells do not mature and function properly, leading to immunodeficiency and dysregulation.2,4 APDS is characterized by severe and recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy.5,6 Because these symptoms can be associated with a variety of conditions, including other primary immunodeficiencies, people with APDS are frequently misdiagnosed and experience a median diagnostic delay of 7 years.7 Because APDS is a progressive disease, this delay can lead to to an accumulation of damage over time, including permanent lung damage and lymphoma.5-8 The only way to definitively diagnose this condition is through genetic testing.

Acerca de leniolisib

Leniolisib is a small molecule inhibitor of the delta isoform of the class IA PI3K 110 kDa catalytic subunit. PI3Kδ is expressed predominantly in hematopoietic cells and is essential for the normal functioning of the immune system through the conversion of phosphatidylinositol-4-5-triphosphate (PIP2) to phosphatidylinositol-3-4-5-triphosphate (PIP3). Leniolisib inhibits the production of PIP3, and PIP3 serves as an important cellular messenger that activates AKT (via PDK1) and regulates a multitude of cellular functions including proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Unlike PI3Kα and PI3Kβ, which are ubiquitously expressed, PI3Kẟ and PI3Kγ are mainly expressed in cells of hematopoietic origin. The central role of PI3Kẟ in the regulation of numerous cellular functions of the adaptive immune system (B cells and, to a lesser extent, T cells), as well as the innate immune system (neutrophils, mast cells, and macrophages), clearly indicates that PI3Kẟ is a target Valid and potentially effective therapeutics for immune diseases such as APDS. To date, leniolisib has been well tolerated during the Phase 1 first-in-human trial in healthy subjects and the Phase II/III registration clearance study in patients with APDS.

Acerca de 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. Pharming is commercializing and developing an innovative portfolio of precision medicines and protein replacement therapies, including small molecules, biologics and gene therapies that are in early or late stages of development. Pharming is headquartered in Leiden, The Netherlands, with employees around the world caring for patients in more than 30 markets in North America, Europe, the Middle East, Africa and Asia-Pacific.

For more information, visit www.pharming.com and find us on LinkedIn.

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. statements. These forward-looking statements are identified by the use of terms and phrases such as "target", "ambition", "anticipate", "believe", "could", "estimate", "expect", ''goals'', '' aim'', ''can'', ''milestones'', ''objectives'', ''outlook'', ''plan'', ''probably'', ''project'', ''risks'', "program," "seek," "should," "target," "will," and similar terms and phrases. Examples of forward-looking statements may include statements regarding the 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, the statements of which 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 their cost ramifications yes; and clinical, scientific, regulatory and technical developments. In light of these risks and uncertainties, and other risks and uncertainties described in Pharming's 2021 Annual Report and Annual Report on Form 20-F for the year ended December 31, 2021, filed with the Commission on In the US Securities and Exchange, 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 by such forward-looking statements. 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. All 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 press release. Pharming assumes no obligation to publicly update or revise any.

internal information

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References

For more public information, contact:

Pharming Group, Leiden, The Netherlands Michael Levitan, Vice President Investor Relations and Corporate Communications T: 1 (908) 705 1696

Heather Robertson, Director of Investor Relations and Corporate CommunicationsE: investor@pharming.com

FTI Consulting, Londres, Reino UnidoVictoria Foster Mitchell/Alex Shaw/Amy ByrneT: 44 203 727 1000

LifeSpring Life Sciences Communication, Ámsterdam, Países BajosLeon MelensT: 31 6 53 81 64 27E: pharming@lifespring.nl

RR. PP. of EE. UU.Ethan MetelenisE: Ethan.Metelenis@precisionvh.comT: 1 (917)

RR. PP. de la UED Dan CaleyE: Dan.caley@aprilsix.comT: 44 (0) 787 546 8942

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