PR95288

LEIDEN, Netherlands, April 2, 2022 /PRNewswire=KYODO JBN/ --

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 (PI3K

delta) 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 (

https://cis.clinimmsoc.org/education/meetings/am22 ).

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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-primary endpoints, which evaluated reduction

in lymph node size and correction of immunodeficiency. The shrinking of

lymphadenopathy lesions and increased proportion of naive B cells are important

in this population, as they indicate a reduction in APDS disease markers.

Presented for the first time at CIS, the co-primary endpoints at day 85 after

baseline demonstrated:

    -- In the index lymphadenopathy lesions, a statistically significant

       adjusted mean change in the log10 transformed sum of product of

       diameters (SPD) of -0.30 among patients who received 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 naive B cells in patients 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 of study treatment, there were no deaths, and the incidence of

serious adverse events (SAEs) was lower in the leniolisib group than in the

placebo group. None of the SAEs were suspected to be related 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 this difficult disease, both

improving care and reducing patients' symptoms. Progress toward a treatment

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 quarter of 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 and was 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 with regulatory authorities

across the globe to make leniolisib available to immunologists, hematologists,

and their patients, we will continue to develop this treatment through our

open-label 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 delta 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 maturation of white blood cells.

Variants of these genes lead to hyperactivity of the PI3K delta

(phosphoinositide 3-kinase delta) pathway.(1,2) Balanced signaling in the PI3K

delta pathway is essential for physiological immune function. When this pathway

is hyperactive, immune cells fail to mature and function properly, leading to

immunodeficiency and dysregulation.(1,3) APDS is characterized by severe,

recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and

enteropathy.(4,5) Because these symptoms can be associated with a variety of

conditions, including other primary immunodeficiencies, people with APDS are

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 of

phosphatidylinositol-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 PI3K alpha and

PI3K beta, which are ubiquitously expressed, PI3K delta and PI3K gamma are

expressed primarily in cells of hematopoietic origin. The central role of PI3K

delta 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, and macrophages) strongly indicates that PI3K delta

is a valid and potentially effective therapeutic target for several 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 to control inflammation in

affected tissues.

Our lead product, RUCONEST(R), 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(R) in the

United States, the European Union and the United Kingdom through our own sales

and marketing 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 PI3K delta, inhibitor), for the treatment

of activated PI3K delta syndrome, or APDS. World-wide rights for leniolisib

were licensed from Novartis AG in 2019. Leniolisib met both of its primary end

points in a registration 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 preclinical development.

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 and commercial prospects,

Pharming's ability to overcome the challenges posed by the COVID-19 pandemic to

the conduct of its business, and Pharming's expectations regarding its

projected working capital requirements and cash resources. These 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 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 forward-looking 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 of

this 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 1000

FTI 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

SOURCE Pharming Group N.V.