PR99112

LEIDEN, Netherlands, Dec. 7, 2022 /PRNewswire=KYODO JBN/--

Leniolisib was well tolerated and significant improvement over placebo was

notable in the co-primary endpoints, reflecting a favorable impact on patients'

immune dysregulation and deficiency

The peer-reviewed publication heightens international understanding of APDS, a

rare and recently characterized immunodeficiency

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

(Nasdaq: PHAR) announces today that the positive results of a Phase 3 clinical

trial of the investigational drug leniolisib, an oral, selective

phosphoinositide 3-kinase delta (PI3K[delta]) inhibitor, in adult and

adolescent patients with activated phosphoinositide 3-kinase delta syndrome

(APDS), a rare primary immunodeficiency, have been published in Blood,1 the

peer-reviewed international medical journal of the American Society of

Hematology (

https://ashpublications.org/blood/article/doi/10.1182/blood.2022018546/493284/Randomized-Placebo-Controlled-Phase-3-Trial-of

). Data from this study was previously announced on February 2, 2022.

The paper, entitled 'Randomized, Placebo-Controlled, Phase 3 Trial of

PI3K[delta] Inhibitor Leniolisib for Activated PI3K[delta] Syndrome', outlined

results from the multinational, triple-blind, placebo-controlled, randomized

clinical trial, which enrolled 31 patients with APDS aged 12 years or older.

Patients were randomly assigned in a 2:1 ratio to receive 70 mg leniolisib or

placebo twice daily for 12 weeks. Improvement over placebo was significant in

the co-primary endpoints which evaluated reduction in lymph node size and

increase in naive B cells, reflecting the impact on immune dysregulation and

correction of immunodeficiency in these patients, respectively. The adjusted

mean change (95% CI) between leniolisib and placebo for lymph node size was

-0.25 (-0.38, -0.12; P=0.0006; N=26) and for percentage of naive B cells was

37.30 (24.06, 50.54; P=0.0002; N=13). Leniolisib was well tolerated, and fewer

patients receiving leniolisib reported study treatment-related adverse events

(mostly grades 1-2) compared to those receiving placebo (23.8% vs 30.0%).

Vicki Modell, co-founder of the Jeffrey Modell Foundation, an international,

non-profit, organization dedicated to helping individuals and family members

affected by primary immunodeficiency disorders, commented:

"Pharming continues to provide significant support for the immunodeficiency

community. The Jeffrey Modell Foundation is dedicated to early diagnosis and

finding meaningful treatments for primary immunodeficiency, and we are acutely

aware of the challenges faced by people with APDS. The publication of study

results in this patient population in such a distinguished and widely read

journal advances these goals."

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

"As we continue to seek a better understanding of APDS as a recently

characterized rare disease, we remain committed to sharing our findings with

researchers and doctors around the world. With this commitment in mind, we are

pleased the results of this Phase III clinical trial in leniolisib have been

published in the flagship journal of the American Society of Hematology.

The APDS patient population, and their families, have lived with unmet needs

and without targeted therapies, and the publishing of this study is an integral

step in improving the patient journey for this community. We are proud to share

these results which demonstrated leniolisib to be a well-tolerated, targeted

therapy for APDS. We thank all of our study participants and investigators for

their efforts and the essential role they played in the development of

leniolisib."

About Activated Phosphoinositide 3-Kinase [delta] 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 maturation of white blood cells. Variants of these

genes lead to hyperactivity of the PI3K[delta] (phosphoinositide 3-kinase

delta) pathway.2,3 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.2,4 APDS is characterized by severe, 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

suffer a median 7-year diagnostic delay.7 As APDS is a progressive disease,

this delay may lead 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.

About Leniolisib

Leniolisib is a small-molecule inhibitor of the delta isoform of the 110 kDa

catalytic subunit of class IA PI3K. PI3K[delta]  is expressed predominately in

hematopoietic cells and is essential to normal immune system function through

conversion of phosphatidylinositol-4-5-trisphosphate (PIP2) to

phosphatidylinositol-3-4-5-trisphosphate (PIP3). Leniolisib inhibits the

production of PIP3 and 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 PI3K[alpha] and PI3K[beta], which are

ubiquitously expressed, PI3K[Gamma] and PI3K[delta]  are expressed primarily in

cells of hematopoietic origin. The central role of PI3K[alpha] 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 PI3[delta] is a valid and

potentially effective therapeutic target for immune diseases such as APDS. 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 in

patients with APDS.

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

(https://www.linkedin.com/company/pharming/).

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 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. 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.

References

[1] Rao VK, et al. Blood. 2022. https://doi.org/10.1182/blood.2022018546.

[2] Lucas CL, et al. Nat Immunol. 2014;15:88-97.

[3] Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.

[4] Nunes-Santos C, Uzel G, Rosenzweig SD. J Allergy Clin Immunol.

2019;143(5):1676-1687.

[5] Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.

[6] Maccari ME, et al. Front Immunol. 2018;9:543.

[7] Jamee M, et al. Clin Rev Allergy Immunol. 2019;May 21.

[8] Condliffe AM, Chandra A. Front Immunol. 2018;9:338.

For further public information, contact:

Pharming Group, Leiden, The Netherlands

Michael Levitan, VP Investor Relations & Corporate Communications

Heather Robertson, Investor Relations & Corporate Communications Manager

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

E: Ethan.Metelenis@precisionvh.com

T: +1 (917) 882 9038

EU PR

Dan Caley

E: Dan.caley@aprilsix.com

T: +44 (0) 787 546 8942

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Source: Pharming Group NV