Synairgen : ATS 2023 SPRINTER Poster Presentation

Clinical Development of Inhaled Interferon Beta-1a (SNG001) for the Treatment of Patients with COVID-19 in the Home and Hospital Settings

P. Monk1, J. Brookes1, V. Tear1, T. Batten2, M. Mankowski3, F. Gabbay3, G. Walters1, D. Davies4, C. Brightling5, M. Kraft6, R. Djukanovic4, S. Holgate4 & T. Wilkinson4

1 Synairgen Research Ltd., UK, 2Veramed, UK, 3TranScrip, UK, 4University of Southampton, UK, 5University of Leicester, UK, 6Mount Sinai Medical Center, New York, USA.

Inhaled Interferon beta (IFN-β) for Severe Viral Lung Infections	Summary of Clinical Development of SNG001 in COVID-19	Substantial Clinical Safety Database from 7 Clinical Trials (Home and Hospital)
• IFN-β is a naturally occurring protein which orchestrates the body's antiviral		• A total of 750 patients have been treated with SNG001, the majority of which had a
defences		confirmed or suspected respiratory viral infection (rhinovirus, influenza, SARS-CoV-2, etc)
• Type I IFN deficiency, due to factors like genetic make up, disease or an aging		• 515 patients had COVID-19; 67 had COPD; and 168 patients had asthma
immune system, is associated with severe viral lower respiratory tract illness		• Favourable safety profile - generally fewer patients on SNG001 reporting any adverse event
• Viruses suppress IFN-β production by cells to evade the host immune response		or any serious adverse event versus patients on placebo. No specific safety signals were seen.
• IFN-β shows antiviral activity in cell-based assays against a broad range of viruses		• Well-tolerated locally (lung) - lack of significant systemic tolerability concerns consistent with
• The aim of the inhaled route of delivery is to restore IFN-β levels at the site of		local delivery and negligible systemic exposure (or ADAs) to SNG001 after inhalation
infection in the lungs, suppressed by the virus or reduced due to host factors, to		Clinical Trial Findings Support Further Clinical Development
drive antiviral responses to clear the virus and to minimise systemic exposure.

% Inhibition

		SARS-CoV-2
100
75
50			"Wuhan-like"
25			(Germany/BavPat1/2020)
		Alpha variant (B.1.1.7)
0			Beta variant (B.1.351)
0.01	0.1	1	10	100
	IFN-β Concentration (IU/mL)

Shedding	/mL)
TCID
	50
Viral	10
(Log

5 4 3 2 1 0

Influenza (pH1N1/09)

of% InfectedCells

0	100	1000
	IFN-β (IU/mL)

RSV (A2)

50

Untreated

40 IFN-β (100IU/mL)

30
20
10
0
0	20	40	60	80
	Hours Post Infection

• There remains a strong clinical rationale for developing inhaled IFN-β as a broad-spectrum antiviral for severe viral lung infections. Clinical trial results including favourable safety profile, support continued investigation of SNG001 in trials in COVID-19 and against seasonal cold and flu viruses evaluating:
• • Prevention of hospitalisation in at risk patients in the home setting
  • Prevention of progression and/or mortality in at risk hospitalised patients
  • Prevention of the development of post viral symptoms (data on long COVID symptoms presented at ID Week 2022)

Antiviral activity of SNG001 (IFN-β) in cell based assays

SG016 Trial Design (Hospital Setting)

SG016 Results

• The graph below shows recovery to 'no limitation of activity' across the 14 day treatment period. Patients treated with SNG001 were more than twice as likely to recover compared to those receiving placebo (p=0.043).
• Whilst not powered to show it there were also trends towards prevention of progression to severe disease and faster hospital discharge (see Table below).
• SNG001 was well-tolerated and had a favourable safety profile.
• These data from the Phase 2 study supported progression to the Phase 3 SPRINTER trial.

SG018 (SPRINTER) Trial Design (Hospital Setting)

SG018 (SPRINTER) Results

• The study did not meet its primary efficacy endpoints of hospital discharge and recovery, most likely due to improvement in SoC since we conducted the Phase 2 study at the start of the pandemic, which may have reduced the window to show a treatment effect.
• There was an encouraging signal for the key secondary endpoint of progression to severe disease or death (26% RRR in ITT, 36% RRR in PP*).
• Post hoc analyses in at risk groups showed stronger treatment effects increasing confidence SNG001 was having a beneficial effect on disease progression.
• SNG001 was well-tolerated and had a favourable safety profile.

ACTIV-2 (A5401) Trial Design (Home Setting)

ACTIV-2 (A5401) Results

• There were no statistically significant differences with respect to safety, symptom resolution, or virology.
• Fewer participants treated with SNG001 were hospitalised
• • 86% RRR (p=0.07; Two-sided Fisher's exact test)
  • There were no deaths in either arm
  • In the SG016 Synairgen Phase 2 study (Home setting), 2/58 (3.4%) placebo patients versus 0/56 (0%) SNG001 patients were hospitalised
• SNG001 was well-tolerated and had a favourable safety profile
• DSMB recommended progression to Phase 3 in October 2021

Progression to severe disease or death

Hospitalisation

8%	86%
relative risk	Placebo

reduction

Acknowledgements

We would like to thank all the patients who have taken part in our clinical trials and the study teams who conducted them.

6%

4%

2%

SNG001

Disclosures

Synairgen is a UK-based biotech company developing inhaled interferon beta (SNG001) as a potential treatment for

Monk et al. (2021) Lancet Respir Med; 9(2):196-206

*The main reason for exclusion from the PP was a failure to take two doses in the first three days.

Monk et al. (2023) ERJ Open Res. 2023;9(2):00605-2022.

0% 7/110 1/110

Placebo SNG001

Treatment

severe viral lung infections (www.Synairgen.com).