Poolbeg Pharma Regulatory News (POLB)

Poolbeg Pharma Plc

Positive Results from POLB 001 LPS Human Challenge Trial

Strong potential for POLB 001 to be a blockbuster treatment for severe influenza

Key Highlights

· POLB 001 resulted in a highly significant reduction in p38 MAP kinase driven cytokines

· POLB 001 treatment exhibited a marked reduction in multiple markers of systemic and local inflammation compared with placebo

· Trial results demonstrate expected utility in severe influenza and other acute inflammatory conditions

2 March 2023 - Poolbeg Pharma (AIM: POLB, OTCQB: POLBF, 'Poolbeg' or the 'Company'), a leading infectious disease focused biopharmaceutical company, announces the data readout from the bacterial lipopolysaccharide ('LPS') human challenge trial for POLB 001, a viral strain agnostic, small molecule immunomodulator being developed to address the unmet medical need arising from severe influenza and other acute inflammatory conditions. POLB 001 was shown to be safe and well tolerated and had a potent effect in systemic and localised inflammatory response in a dose dependent manner.

About the LPS Challenge Trial

A total of 36 healthy volunteers aged 18 to 55 were enrolled and completed the trial. Subjects treated with POLB 001 exhibited a marked reduction in multiple markers of systemic and localised inflammation compared with placebo. p38 MAPK target engagement within circulating blood cells caused a substantial ablation of blood cytokines which are synonymous with cytokine release syndrome ('CRS') common in severe influenza, patients receiving CAR T cell treatment and other acute inflammatory conditions.

Systemic Inflammatory Response

The typical LPS-induced rise in plasma cytokine levels (TNF-α, IL-6, and IL-8) decreased between 57-81% across all cytokines in subjects treated with 70 mg or 150 mg POLB 001 (all highly significant P values

POLB 001 was shown to have the following dose dependent effects:

- blunted the LPS associated rise in heart rate across all dose groups (P

- reduced body temperature and C-reactive protein ('CRP') levels, a clinically used nonspecific marker of inflammation

- target engagement causing a dose dependent reduction in p38 phosphorylation activation status in white blood cells

Localised Inflammatory Response

POLB 001 infiltration into inflamed tissues blocked localised cytokine release and reduced invasion of tissue damaging inflammatory cells as reflected by:

- complete ablation of tissue damaging neutrophil accumulation within the inflamed tissue

- LPS-induced rise in intermediate monocytes (inflammatory mediators) was substantially lower in subjects treated with 70 mg or 150 mg POLB 001

- a highly significant reduction in TNF-α in subjects treated with 150 mg POLB 001 of 65.1% (P

Virtual Company presentation

Jeremy Skillington, PhD, Chief Executive Officer, David English, VP of Business Development and key opinion leader Derek Gilroy, PhD, Professor of Immunology at University College London, will provide a live presentation via the Investor Meet Company platform on Thursday 2 March 2023 at 10am. Click here to register.

The presentation is open to analysts and all existing and potential shareholders. Investors can sign up to Investor Meet Company for free and add to meet Poolbeg Pharma plc here. The presentation and recording will be available on the Company's website after the event here.

Jeremy Skillington, PhD, Chief Executive Officer, Poolbeg Pharma, said: "Together these data indicate POLB 001 reaches all cells and tissues where p38 MAPK is expressed, shutting down inflammation and silencing multiple aspects of overactivated inflammation unlike many anti-inflammatory drugs that target a single immune pathway.

POLB 001 blocks inflammation both locally and systemically and in a manner that suggests efficacy in treating life-threatening infections such as severe influenza or the CRS associated with other acute inflammatory conditions. POLB 001 has the potential to be an effective treatment in a wide range of inflammatory syndromes that present serious and life-threatening complications for patients. Due to our parallel clinical programs with POLB 001 we are particularly excited that these results support continued clinical investigation in both indications, and that we can share this positive data with potential Pharma partners ahead of schedule."

Derek Gilroy, Ph.D, Professor of Immunology at University College London, said: "The COVID-19 pandemic, more than anything in recent memory, has shown how bereft we are of the medicines needed to treat infections, and stop our immune system from killing us. With such pandemics increasing in frequency, it's only a matter of time before we face yet another crisis.

Poolbeg Pharma has risen to this challenge. POLB 001 has shown substantial promise in dampening the key players of harmful inflammation in both blood and tissues, acting where the immune system can do harm. These exciting data, and safety profile, support a role for POLB 001 beyond infectious diseases into treating a range of acute, aggressive immune responses."

About POLB 001 and the LPS Human Challenge Trial

POLB 001 is a small molecule immunomodulator for the treatment of cytokine release syndrome (CRS) related conditions such as severe influenza and other acute inflammatory conditions. POLB 001 selectively inhibits overwhelming inflammation in viral infections, such as influenza, while leaving the necessary immune functions intact to fight the infection. This contrasts with other immunomodulatory approaches, such as steroids, which affect both beneficial and damaging immune responses. Due to its mode of action it is strain agnostic and unaffected by seasonal variants which is a significant advantage over treatments available on the market. In addition, as a shelf stable oral drug it is an ideal stock piling candidate for both seasonal and pandemic outbreaks. Therefore, POLB 001 has the potential to be a transformational treatment for patients and to become a leading severe influenza treatment.

Cytokines, originally intended to optimise immunity, when overexpressed can sweep throughout the body re-programming white blood cells causing tissue damage, shutting down circulation and other essential organs leading to death; a process called septic shock and in certain circumstances cytokine storm or cytokine release syndrome (CRS). Such excessive cytokine responses can be seen in diseases such as severe influenza and in response to chimeric antigen receptor T cell therapy (CAR T cell) treatment of cancers. Poolbeg continues to evaluate POLB 001's potential in additional indications to fully unlock the potential value of the molecule.

p38 MAP kinase (p38 MAPK) is a master regulator of immunity, ubiquitously expressed in all white blood cells where it is poised to unleash inflammation. Poolbeg's clinical approach, inhibiting p38 MAP kinase hypothesised that it's a prime suspect in driving the cytokine storm and its consequences. This has now been demonstrated as a concept in a human clinical model of infectious disease and endotoxin mediated inflammation administering LPS as the endotoxin to healthy volunteers. LPS is a bacterial product that mimics infection and is used to capture the hallmarks of both local and systemic inflammation typical of a cytokine storm in humans, but in a safe, controlled and quantifiable manner - it's one step removed from the infected critical care patient. The trial was conducted at the Centre for Human Drug Research (CHDR) in the Netherlands with Principal Investigator Dr Matthijs Moerland.

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About Poolbeg Pharma

Poolbeg Pharma specialises in the development of innovative medicines to address the unmet need in prevalent and emerging infectious diseases. Poolbeg has a disciplined portfolio approach to mitigate risk, accelerate drug development and enhance investor returns. The Company simultaneously advances multiple programmes in cost-effective clinical trials, rapidly generating early human safety and efficacy data to enable early partnering / out-licensing, with the funds generated reinvested in the pipeline. Poolbeg also uses AI to interrogate human challenge trial data sets to quickly identify new targets and drugs, and in-license near or in the clinic medicines, leading to faster development and greater commercial appeal.

The Company is targeting the growing infectious disease market. In the wake of the COVID-19 pandemic, infectious disease has become one of the fastest growing pharma markets and is expected to exceed $250bn by 2025.

With its initial assets from hVIVO plc (formerly Open Orphan plc), an industry leading infectious disease and human challenge trials business, Poolbeg has access to knowledge, experience, and clinical data from over 20 years of human challenge trials. The Company is using these insights to acquire new assets as well as reposition clinical stage products, reducing spend and risk. Amongst its portfolio of exciting assets, Poolbeg has a small molecule immunomodulator for severe influenza and other acute inflammatory conditions (POLB 001) which produces a highly significant reduction in p38 MAP kinase driven cytokines in a clinical setting; a first-in-class, intranasally administered RNA-based immunotherapy for respiratory virus infections (POLB 002); and a vaccine candidate for Melioidosis (POLB 003). The Company is also developing two Oral Delivery Programmes and is progressing two Artificial Intelligence (AI) Programmes to add promising new assets to its pipeline.

For more information, please go to www.poolbegpharma.com or follow us on Twitter and LinkedIn @PoolbegPharma.