Setting the standard: unique long-term control of the immune response

PIN201104 (‘1104)

‘1104 uniquely reduces three key cells involved in both allergic and non-allergic inflammation: eosinophils, neutrophils and lymphocytes.

Successfully delivered by intravenous bolus injection, sub-cutaneous injection and intra-nasal administration in studies to date, ‘1104 has the potential to be the first IMRAD (IMmune Resetting Asthma Drug) with activity independent of the allergic cause of asthma.

Early development

Chaperonin 60.1 is secreted by Mycobacterium tuberculosis, which has evolved to produce specific proteins that demonstrate immunomodulatory effects, reducing the body’s natural immune responses of inflammation and hypersensitivity to ensure the bacteria can survive for decades within the human lung. Chaperonin 60.1 has been shown to be associated with a 5-fold reduction in the prevalence or risk of developing asthma or allergy in people infected with tuberculosis (TB), with latent TB or who have had the BCG vaccination (literature meta-analysis).1-5

‘1104 is a low molecular weight peptide derived from chaperonin 60.1 with similar activities to the parent tuberculosis bacterium protein. The original key observations and fundamental research came about through a collaboration between two leading British universities: King’s College, London and St George’s University, London. Following extensive investigation and development by Immune Regulation (formerly Peptinnovate), ‘1104 entered phase 1 clinical development in January 2017 as a first-in-class potential disease modifier of asthma and for treatment of other inflammatory diseases.

Preclinical and clinical studies

Preclinical studies in a house dust mite re-challenge model showed that ‘1104, given as a single administration at the time of challenge, reduced inflammatory response to allergen re-challenge for at least 14 days later in mice sensitised to be allergic to house dust mite, despite the compound being metabolised within a few hours (blood half-life, 10 minutes). These data suggest that ‘1104 is capable of modulating the immune response long after complete systemic clearance, suggesting that long term disease remission of asthma could be possible with ‘1104.

 

When compared to commonly used treatments, neither the steroid treatment, fluticasone furoate, nor the leukotriene antagonist, montelukast, were able to reduce inflammatory response to allergen re-challenge at 14 days, as would be expected following complete drug clearance. The anti-IL5 antibody is specifically targeted at eosinophils and showed a reduction on only this cell type at 14 days due to the antibody remaining present in the system at this time point.

In a Phase I, randomised, double-blind, placebo-controlled, parallel group study in healthy volunteers and patients with asthma to assess the safety, tolerability, and pharmacokinetics of single ascending and repeat doses of ‘1104, ‘1104 demonstrated a good tolerability profile with no major safety or toxicity signals.

Two Phase II studies of ‘1104 are expected to begin during 2019:

 

 

‘1104 is covered up to 2029/30 by a composition of matter patent in the major markets, not including potential extensions or additions.