PR98058

LEIDEN, The Netherlands, Sep 28, 2022, /PRNewswire=KYODO JBN/--

The FDA has assigned a PDUFA goal date of March 29, 2023 for the NDA submission

based on randomized-controlled and long-term extension data for leniolisib as a

treatment for APDS, a rare primary immunodeficiency

Pharming Group N.V. ("Pharming" or "the Company") (Euronext Amsterdam: PHARM)

(Nasdaq: PHAR) announces that the US Food and Drug Administration (FDA) has

accepted for priority review its New Drug Application (NDA) for leniolisib, an

oral, selective phosphoinositide 3-kinase delta (PI3Kdelta) inhibitor, to treat

the rare primary immunodeficiency activated phosphoinositide 3-kinase delta

syndrome (APDS) in adults and adolescents 12 years of age and older in the US.

The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of

March 29, 2023, aligned with a Priority Review classification.

Submitted by Pharming on July 29, 2022, the NDA was supported by positive data

from a Phase II/III study of leniolisib, which met its co-primary endpoints of

reduction in index lymph node size and correction of immunodeficiency in the

target population. Those results demonstrated the efficacy of leniolisib over

placebo with a statistically significant reduction from the baseline size of

participants’ index lymphadenopathy lesions (p=0.006) and normalization of

their immune function, as evidenced by an increased proportion of naïve B cells

from the baseline (p=0.002). Those findings indicate a reduction in disease

markers associated with APDS, whose clinical hallmarks include significant

lymphoproliferation and immune dysfunction, as well as increased risk of

lymphoma. Furthermore, safety data from the study showed that leniolisib was

well tolerated by participants. Also submitted as part of the application were

data from a long-term, open-label extension clinical trial including 38

patients with APDS who were treated with leniolisib for a median of 102 weeks.

Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented:

"The FDA's acceptance for priority review of Pharming's New Drug Application

for leniolisib is a milestone that demonstrates our commitment to addressing

unmet needs for patients with rare diseases. With FDA’s review, leniolisib

moves further along the regulatory pathway as a potential disease-modifying

targeted treatment for APDS in adults and adolescents 12 years of age and older

in the US, who currently rely on supportive therapies such as antibiotics and

immunoglobulin replacement therapy. We look forward to continuing to work

closely with the FDA, as well as with regulatory authorities across the globe,

to make leniolisib available to immunologists, hematologists, and their APDS

patients."

About Activated Phosphoinositide 3-Kinase delta Syndrome (APDS)

APDS is a rare primary immunodeficiency that affects approximately 1 to 2

people per million. 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 PI3Kdelta (phosphoinositide 3-kinase delta)

pathway.1,2 Balanced signaling in the PI3Kdelta 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 activating AKT (via PDK1) and regulates a multitude of cell

functions such as proliferation, differentiation, cytokine production, cell

survival, angiogenesis, and metabolism. Unlike PI3Kalpha and PI3Kbeta, which

are ubiquitously expressed, PI3Kdalta and PI3Kgaba are expressed primarily in

cells of hematopoietic origin. The central role of PI3Kdelta 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 PI3Kdelta 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. (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 protein replacement therapies and

precision medicines, including small molecules, biologics, and gene therapies

that are in early to late-stage development. Pharming is headquartered in

Leiden, Netherlands, and has employees around the globe who serve patients in

over 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 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, 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 and

technical developments. In light of these risks and uncertainties, and other

risks and uncertainties that are described in Pharming’s 2021 Annual Report and

the Annual Report on Form 20-F for the year ended December 31, 2021 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.

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.

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

Heather Robertson, Investor Relations & Corporate Communications Manager

T: +31 71 524 7400

E: investor@pharming.com

FTI Consulting, London, UK

Victoria Foster Mitchell/Alex Shaw/Amy Byrne

T: +44 203 727 1000

LifeSpring Life Sciences Communication, Amsterdam, The Netherlands

Leon Melens

T: +31 6 53 81 64 27

E: pharming@lifespring.nl

US PR:

Ethan Metelenis

T: +1 (917) 882 9038

E: Ethan.Metelenis@precisionvh.com

EU PR:

Dan Caley

T: +44 (0) 787 546 8942

E: Dan.caley@aprilsix.com

SOURCE: Pharming Group N.V.