Pharming Announces Positive Data from Phase II/III Leniolisib Trial
Presented at Clinical Immunology Society 2022 Annual Meeting
Leiden, the Netherlands, April 1, 2022: Pharming Group N.V. (“Pharming” or “the Company”)(EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) announces new data from the pivotal Phase
II/III trial of leniolisib for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ)syndrome (APDS), a primary immunodeficiency. Principal Investigator V. Koneti Rao, M.D., a staff
physician in the Primary Immune Deficiency Clinic at the National Institutes of Health in Bethesda,Maryland, shared the findings in a presentation at the Clinical Immunology Society (CIS) 2022
Annual Meeting.
As announced on February 2, 2022, the multinational, triple-blind, placebo-controlled,randomized, Phase III portion of the clinical trial, conducted by Novartis, met its co-primaryendpoints, which evaluated reduction in lymph node size and correction of immunodeficiency.
The shrinking of lymphadenopathy lesions and increased proportion of naïve B cells are importantin this population, as they indicate a reduction in APDS disease markers. Presented for the firsttime at CIS, the co-primary endpoints at day 85 after baseline demonstrated:••

In the index lymphadenopathy lesions, a statistically significant adjusted mean change inthe log10 transformed sum of product of diameters (SPD) of -0.30 among patients whoreceived leniolisib compared with -0.06 among patients who received placebo (95% CI: 0.37, -0.11; p=0.0012).
From a baseline level of ˂48%, an increase of 34.76% in the proportion of naïve B cells inpatients who received leniolisib versus a -5.37% decrease in patients who received
placebo (95% CI: 28.51, 51.75; p˂0.0001).

The study drug was well-tolerated. There were no adverse events that led to discontinuation ofstudy treatment, there were no deaths, and the incidence of serious adverse events (SAEs) waslower in the leniolisib group than in the placebo group. None of the SAEs were suspected to berelated to study treatment.
Charlotte Cunningham-Rundles, M.D., Ph.D., David S. Gottesman Professor of Immunology at
the Mount Sinai School of Medicine in New York, said:“It is great news that leniolisib has achieved such positive results in this Phase III study in APDS.
It is extremely encouraging to see that this medication is capable of targeting the cause of thisdifficult disease, both improving care and reducing patients’ symptoms. Progress toward atreatment that is tailor-made for our patients with APDS is a milestone we have long awaited.”Pharming plans to begin submitting global regulatory filings for leniolisib in the second quarterof 2022 and, subject to approval, launching the treatment in the U.S. in the first quarter of 2023
and starting a series of European launches in the second half of 2023.
Anurag Relan, Chief Medical Officer of Pharming, commented:“Pharming is delighted that leniolisib achieved significance in both co-primary endpoints andwas well tolerated in these APDS patients, as the product’s approval would address an unmet
need for those with this rare disease, who currently rely on supportive therapies such as
antibiotics and immunoglobulin replacement therapy. In addition to working closely withregulatory authorities across the globe to make leniolisib available to immunologists,
hematologists, and their patients, we will continue to develop this treatment through our openlabel extension study and two additional studies that will enroll children under the age of 12, as
well as potentially extending the geographic reach of the product.”About Activated Phosphoinositide 3-Kinase δ Syndrome (APDS)
APDS is a rare primary immunodeficiency that affects approximately one to two people per million. Also
known as PASLI, it is caused by variants in either of two genes, PIK3CD or PIK3R1, that regulate maturationof white blood cells. Variants of these genes lead to hyperactivity of the PI3Kδ (phosphoinositide 3-kinasedelta) pathway.1,2 Balanced signaling in the PI3Kδ pathway is essential for physiological immune function.
When this pathway is hyperactive, immune cells fail to mature and function properly, leading toimmunodeficiency and dysregulation.1,3 APDS is characterized by severe, recurrent sinopulmonary
infections, lymphoproliferation, autoimmunity, and enteropathy.4,5 Because these symptoms can beassociated with a variety of conditions, including other primary immunodeficiencies, people with APDSare frequently misdiagnosed and suffer a median 7-year diagnostic delay.6 As APDS is a progressive
disease, this delay may lead to an accumulation of damage over time, including permanent lung damage
and lymphoma.4-7 The only way to definitively diagnose this condition is through genetic testing.
About leniolisib
Leniolisib is a small-molecule inhibitor of the delta isoform of the 110 kDa catalytic subunit of class IA PI3K
with immunomodulating and potentially anti-neoplastic activities. Leniolisib inhibits the production ofphosphatidylinositol-3-4-5-trisphosphate (PIP3). PIP3 serves as an important cellular messenger
specifically activating AKT (via PDK1) and regulates a multitude of cell functions such as proliferation,differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Unlike PI3Kα and PI3Kβ,
which are ubiquitously expressed, PI3Kẟ and PI3Kγ are expressed primarily in cells of hematopoietic origin.
The central role of PI3Kẟ in regulating 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, andmacrophages) strongly indicates that PI3Kẟ is a valid and potentially effective therapeutic target forseveral immune diseases.
To date, leniolisib has been well tolerated during both the Phase 1 first-in-human trial in healthy subjects
and the Phase II/III registration-enabling study.

About Pharming Group N.V.
Pharming Group N.V. is a global, commercial stage biopharmaceutical company developing innovative
protein replacement therapies and precision medicines for the treatment of rare diseases and unmet
medical needs.
The flagship of our portfolio is our recombinant human C1 esterase inhibitor (rhC1INH) franchise. C1INH
is a naturally occurring protein that down regulates the complement and contact cascades in order tocontrol inflammation in affected tissues.
Our lead product, RUCONEST®, is the first and only plasma-free rhC1INH protein replacement therapy. It
is approved for the treatment of acute hereditary angioedema (HAE) attacks. We are commercializing
RUCONEST® in the United States, the European Union and the United Kingdom through our own sales andmarketing organization, and the rest of the world through our distribution network.
In addition, we are investigating the clinical efficacy of rhC1INH in the treatment of further indications,including pre-eclampsia, acute kidney injury and severe pneumonia as a result of COVID-19 infections.
We are also studying our oral precision medicine, leniolisib (a phosphoinositide 3-kinase delta, or PI3Kdelta, inhibitor), for the treatment of activated PI3K delta syndrome, or APDS. World-wide rights forleniolisib were licensed from Novartis AG in 2019. Leniolisib met both of its primary end points in aregistration enabling Phase 2/3 study in the United States and Europe. We are targeting global regulatory
filings for leniolisib from Q2 2022 onwards.
Additionally, we entered into a strategic collaboration with Orchard Therapeutics to research, develop,
manufacture and commercialize OTL-105, a newly disclosed investigational ex-vivo autologous
hematopoietic stem cell (HSC) gene therapy for the treatment of HAE.
Furthermore, we are leveraging our transgenic manufacturing technology to develop next-generation
protein replacement therapies, most notably for Pompe disease, which is currently in preclinicaldevelopment.
Forward-looking Statements
This press release contains forward-looking statements, including with respect to timing and progress of
Pharming’s preclinical studies and clinical trials of its product candidates, Pharming’s clinical andcommercial prospects, Pharming’s ability to overcome the challenges posed by the COVID-19 pandemic tothe conduct of its business, and Pharming’s expectations regarding its projected working capitalrequirements and cash resources. These statements are subject to a number of risks, uncertainties andassumptions, 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 and technical developments. In
light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming’s
2020 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2020 filed with
the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forwardlooking statements may not occur, and Pharming’s actual results could differ materially and adversely

from those anticipated or implied thereby. Any forward-looking statements speak only as of the date ofthis press release and are based on information available to Pharming as of the date of this release.
References:
1. Lucas CL, et al. Nat Immunol. 2014;15:88-97.
2. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.
3. Nunes-Santos C, Uzel G, Rosenzweig SD. J Allergy Clin Immunol. 2019;143(5):1676-1687.
4. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.
5. Maccari ME, et al. Front Immunol. 2018;9:543.
6. Jamee M, et al. Clin Rev Allergy Immunol. 2019;May 21.
7. Condliffe AM, Chandra A. Front Immunol. 2018;9:338.

For further public information, contact:
Pharming Group, Leiden, The Netherlands
Sijmen de Vries, CEO: T: +31 71 524 7400
Susanne Embleton, Investor Relations Manager: T: +31 71 524 7400 E: investor@pharming.com
FTI Consulting, London, UK
Victoria Foster Mitchell/Alex Shaw
T: +44 203 727 1000FTI Consulting, USA
Jim Polson
T: +1 (312) 553-6730
LifeSpring Life Sciences Communication, Amsterdam, The Netherlands
Leon Melens
T: +31 6 53 81 64 27
E: pharming@lifespring.nl
US PR:Emily VanLare
E: Emily.VanLare@precisionvh.com
T: +1 (203) 985 5596
EU PR:

Dan Caley
E: Dan.caley@aprilsix.com
T: +44 (0) 787 546 8942