Press Release: Santhera and Cold Spring Harbor Laboratory to Investigate Lonodelestat (POL6014) in COVID-19-related Acute Respiratory Distress Syndrome (ARDS)

Pratteln, Switzerland, April 27, 2020 -- Santhera Pharmaceuticals (SIX:

SANN) has entered into a collaboration agreement with Cold Spring Harbor

Laboratory (CSHL) to investigate the potential of lonodelestat (POL6014),

a potent inhibitor of human neutrophil elastase (hNE), as a therapeutic

intervention for COVID-19-related acute respiratory distress syndrome

(ARDS).

Researchers at CSHL are part of a recently formed consortium of

international non-clinical and clinical experts called the 'NETwork to

target neutrophils in COVID-19'. This NETwork will study the role of

neutrophils and neutrophil extracellular traps (NETs) in the pathology

of COVID-19 as well as hNE and other targets for intervention for the

purpose of treating COVID-19 [1, 2].

NETs are macromolecular structures of DNA and proteins that neutrophils

can expel, for example during severe inflammation. hNE is released by

neutrophils when they form NETs. There are clear similarities between

the clinical presentation of severe COVID-19 and diseases known to

involve NETs, such as ARDS. On this basis, the NETwork has developed the

rationale that excess NETs may play a major role in COVID-19 and that

inhibition of hNE may be a therapeutic strategy to antagonize NETs in

COVID-19 patients.

Santhera will provide lonodelestat and intellectual support for the

scientists at CSHL who will conduct the non-clinical research program.

The work is expected to further validate hNE as a target and shed light

on this clinical stage compound as a potential agent also in COVID-19.

"There is a strong scientific rationale that inhibition of hNE may

interrupt a neutrophil-driven inflammatory cascade that leads to ARDS in

COVID-19 patients" explained Mikala Egeblad, PhD, Associate Professor at

Cold Spring Harbor Laboratory, New York. "Based on previous work with

lonodelestat in models of ARDS and acute lung injury, we were very

encouraged about the potential of lonodelestat. Our own research in

non-clinical models will start immediately and we are delighted that

Santhera has offered their support in our efforts to find a potential

novel treatment that could be investigated in patients with COVID-19."

"We would like to thank CSHL and collaborating clinicians that have

approached us to support their efforts to further explore and understand

the role of hNE in relation to ARDS in COVID-19," said Kristina

Sjöblom Nygren, MD, Chief Medical Officer and Head of Development

of Santhera.

About lonodolestat (POL6014)

Lonodelestat (previously known as POL6014) is a highly potent and

selective peptide inhibitor of human neutrophil elastase (hNE). In

preclinical studies lonodelestat was effective in animal models of

neutrophil activation in lung tissue and of acute lung injury (ALI) [3,

4]. Lonodelestat is an investigational drug which completed Phase 1

single dose escalation studies in healthy volunteers and patients with

cystic fibrosis (CF) and is currently investigated in a multiple

ascending dose study in CF patients. Current data demonstrated that

single dose inhalation of lonodelestat can lead to high drug

concentrations within the lung, resulting in inhibition of hNE in sputum

of patients, an enzyme associated with lung tissue inflammation [5].

References:

[1] Global NETwork studies role of immune cells in COVID-19 deaths,

https://www.globenewswire.com/Tracker?data=SMfi8zwWN41-Q3xee8UfUeyU_BCfwe5qDvCAvDJBrjNGf-ukNhXE8wzy_JSxojNm3PXgccfiC8l6mSiIzd8jLvEYT_BgvZhCws24xgRm90vxQGValKnlcsW5CXFShhECi_PzSI3yHgl91cGa12MBnMYzsTrBp4Hnx_pw8nyoRiKEQQIiGRbzQ0nbzkIoanQ2

CSHL Stories and Media

[2] Barnes B J et al (2020). Targeting potential drivers of COVID-19:

Neutrophil extracellular traps.

https://www.globenewswire.com/Tracker?data=1qB4KqVtl5q7eChj3ojxqYWq4P68BWfU2QbVYjSYljZ6ImZycfd_1uE7JOyYYkC8MQ_3Hq-jorgKyefpbuzJ3IuaNKTMLHyiXxSfdyJIGddi-PI-Tyx8QPRMSSQGEaTHBCOJ4aRULJYPw4AMSDxXPCe291iQcrzGDabO-NhILLs9uzkOuqx-kQSzT7FGtETZpB8XknVgNhoFrWB8qbJbV3U9q1MhDKhUblgRVE88EiA=

J Exp Med (2020) 217 (6): e20200652. DOI:

https://doi.org/10.1084/jem.20200652

[3] Sellier Kessler O et al (2018). Effect of POL6014, a Potent and

Selective Inhaled Neutrophil Elastase Inhibitor, in a Rat Model of Lung

Neutrophil Activation.

https://www.globenewswire.com/Tracker?data=HJxD1nRBEeb9GHB5_IaK5rAS8VYbi1VFgYuKN25mf4aX2qbwtMYu5x7p90Y8XPti-Y4ELiCeQ00RSB_cexZ5opAlQyeBpF7X1vyzGIpHO7BXV-nqmlu7BdCvk3edom7p-Y2syygvYWMnUMkD24Qd_KmGroybqsbtAh3uHF07FxJt9IiFHCPAGtA1jCNEBd6_d0JWD-MaVN5LOZ7zrPMVI8szYjgXSy6FxVNArwc24zw=

Am. J. Respir. Crit. Care Med. 2018; 197: A2988

[4] Lagente V et al (2009) A Novel Protein Epitope Mimetic (PEM)

Neutrophil Elastase (NE) Inhibitor, POL6014, Inhibits Human NE-Induced

Acute Lung Injury in Mice.

https://www.globenewswire.com/Tracker?data=HJxD1nRBEeb9GHB5_IaK5rAS8VYbi1VFgYuKN25mf4ZzuNk-y0o-lpRGJI-uAT3JoQl2xlyVAbXhv8GbmvMTy7rSfizHjdD4mmnDqBgKDN3sOc3j4Ss90bxnu6PSpStmE3_ut560TZJER2tvEyuHtlXmp27CAOoETlR2BqrL260nucirz8SpfnYAG-b7mDvtVlckhdJNpjXJRdkjiJW8RZmjfM9liJha_WjxIzNSm5I=

Am. J. Respir. Crit. Care Med. 2009; 179: A5668

[5] Barth P. et al (2019). Single dose escalation studies with inhaled

POL6014, a potent novel selective reversible inhibitor of human

neutrophil elastase, in healthy volunteers and subjects with cystic

fibrosis.

https://www.globenewswire.com/Tracker?data=rpG0eh8m7PDp-8nwgp66XdZ6WVwO3RzCZlPcgc4rPJ9yQMLfyQGOl1oe_24dULBhQPRR_gT0q6JyFCJl03sExpsju0BKmU1ceplsieAUohvmVB_RdglOV6CJwIzAIhha

Journal of cystic fibrosis 2019. DOI:

https://doi.org/10.1016/j.jcf.2019.08.020

About human neutrophil elastase (hNE), acute respiratory distress

syndrome (ARDS) and COVID-19

Activated or necrotic neutrophils liberate human neutrophil elastase

(hNE) in the lung which causes damage to the pulmonary microenvironment.

hNE is also a critical enzyme in neutrophils and it is required for

neutrophils to form NETs (neutrophil extracellular traps) as part of the

body's immune response. Under conditions of severe inflammation,

neutrophils can expel NETs which can aggravate pulmonary inflammation

and may contribute to the development of acute respiratory distress

syndrome (ARDS). Inhibition of hNE activity may therefore display a dual

action: it may block the toxicity of hNE in the lung tissue, prevent the

formation of NETs and therefore may allow combating ARDS in patients

with COVID-19.

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary

biomedical research and education with programs in cancer, neuroscience,

plant biology and quantitative biology. Home to eight Nobel Prize

winners, the private, not-for-profit Laboratory is a National Cancer

Institute designated Cancer Center employing 1,100 people including 600

scientists, students and technicians. The Meetings & Courses Program

hosts more than 12,000 scientists from around the world each year on its

campuses in Long Island and in Suzhou, China. The Laboratory's education

arm also includes an academic publishing house, a graduate school and

programs for middle and high school students and teachers. For more

information, visit

https://www.globenewswire.com/Tracker?data=RFUc962RIXYm-l8DgH1czdYC1e3yEt7k8DyS6Pkur123LYdWs-3ipnH2joix3BPOX2ypKeCHbZzyD-c18PCpKA==

www.cshl.edu

About the 'NETwork to target neutrophils in COVID-19'

In the urgent battle to treat COVID-19 patients, a group of eleven

international medical research organizations is investigating whether

overactive immune cells -- specifically neutrophils -- via production of

neutrophil extracellular traps (NETs) cause the most severe cases. The

group, called the NETwork, includes Cold Spring Harbor Laboratory, the

Feinstein Institutes for Medical Research, McGill University Health

Centre, Weill Cornell Medicine, Donald and Barbara Zucker School of

Medicine at Hofstra/Northwell, Centre Hospitalier Universitaire de Nancy,

University of Michigan, University of California, San Francisco,

University of Texas MD Anderson Cancer Center, University of Utah School

of Medicine, and Northwell Health [1].

About Santhera

Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical

company focused on the development and commercialization of innovative

medicines for rare neuromuscular and pulmonary diseases with high unmet

medical need. Santhera is building a Duchenne muscular dystrophy (DMD)

product portfolio to treat patients irrespective of causative mutations,

disease stage or age. A marketing authorization application for

Puldysa(R) (idebenone) is currently under review by the European

Medicines Agency. Santhera has an option to license vamorolone, a

first-in-class anti-inflammatory drug candidate with novel mode of

action, currently investigated in a pivotal study in patients with DMD

to replace standard corticosteroids. The clinical stage pipeline also

includes lonodelestat (POL6014) to treat cystic fibrosis (CF) and other

neutrophilic pulmonary diseases, as well as omigapil and an exploratory

gene therapy approach targeting congenital muscular dystrophies.

Santhera out-licensed ex-North American rights to its first approved

product, Raxone(R) (idebenone), for the treatment of Leber's hereditary

optic neuropathy (LHON) to Chiesi Group. For further information, please

visit

https://www.globenewswire.com/Tracker?data=RFUc962RIXYm-l8DgH1czf2PVKrzdiv4C-6QT41tqYHR9l5klAboIEZ-dliIGzkXTVnjHBbt5TYY5suSQ2CYHA==

www.santhera.com.

Raxone(R) and Puldysa(R) are trademarks of Santhera Pharmaceuticals.

For further information please contact:

https://www.globenewswire.com/Tracker?data=FR5pQFrXDP9gDvIf5Tpmvf6-cEFvFiIv4SOHPQu9RdV1G2qsiEpUGprmIYuUD8FKqSV_ZzhwOYxhhXNW9arJ9uia3noeBbCkxp8pxYbGUO_Ye6B5UsSUAAjx9avBpe7A

public-relations@santhera.com or

Eva Kalias, Head External Communications

Phone: +41 79 875 27 80

eva.kalias@santhera.com

Disclaimer / Forward-looking statements

This communication does not constitute an offer or invitation to

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April 27, 2020 01:00 ET (05:00 GMT)