Immune Regulation presents new data on ‘1104 at the American Thoracic Society (ATS) Annual International Conference

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Immune Regulation Limited (‘Immune Regulation’ or the ‘Company’) a biopharmaceutical company developing “first in class” immune-resetting therapies for asthma and other inflammatory diseases, publically presented exciting preclinical data on IRL201104 (formerly PIN201104 or ‘1104) for the first time at the annual American Thoracic Society (ATS) International Conference in Dallas, Texas, held on 17th-22nd May.

The ATS Annual Conference is one of the leading pulmonary care (including allergy/immunology) events of the year attracting over 14,000 leading healthcare professionals from around the world.

The data was presented as part of the session titled, “Mechanisms for Airway Hyperresponsiveness: From Cell to Organism”. This is the first public presentation of data from two key preclinical studies. The data shows the activity of ‘1104 in reducing the levels of key inflammatory cells following challenge with two different allergens, and the longer-term immune resetting effects of ‘1104 upon allergen rechallenge with no drug present, due to its short pharmacokinetic half life (10 mins). A copy of the presentation abstract is included below.

In the first study, mice were sensitized to the allergen, ovalbumin (OVA), and treated with ‘1104 during sensitization or following OVA challenge. Allergen rechallenge was performed 10 days after the last ‘1104 treatment. Inflammatory cells were measured 24 hours after initial OVA challenge and after rechallenge. ‘1104 significantly inhibited eosinophil recruitment to the lung 24 hours after sensitization and 10 days after the last treatment on rechallenge.

In the second study, mice were sensitized to house dust mite (HDM) allergen. After two weeks either a single dose of ‘1104 or a control was administered, prior to a first HDM challenge. 14 days later, inflammatory cell recruitment and cytokine release were measured four hours after a second challenge with HDM. Following this HDM rechallenge, ‘1104 markedly reduced levels of three key inflammatory cells, eosinophils, neutrophils and lymphocytes. ‘1104 also reduced levels of pro-inflammatory cytokines (IL-4, IL-5 and IL-13). In contrast, fluticasone, montelukast or anti-IL-5 (other than reduced eosinophils for the anti-IL5) had no significant effect at this time point.

The presentation concluded that ‘1104 significantly inhibited the recruitment of inflammatory cells to the lung in two models of allergic inflammation. The very short exposure time of IRL201104, the prolonged nature of inhibition of cell recruitment, and the reduction in Th-2 cytokines, all suggest that ‘1104’s effects are novel and likely due to a resetting of immune homeostasis.

Richard Nagle, CEO of Immune Regulation commented,
“We are very pleased to release these data to the medical community, confirming our vision for ‘1104 as a short acting molecule, which can potentially have long term effects by resetting the immune system to a normal regulatory state in allergy and asthma. On behalf of Immune Regulation, I would like to thank our academic and industry collaborators who were responsible for performing these studies”.

PIN201104, A Peptide Derived from Mycobacterium Tuberculosis Chaperonin 60.1 Shows Prolonged Modulation of Allergic Inflammation in Murine Lungs

Authors
C. P. Page, D. Federici-Canova, A. Lightfoot, N. Cooper, C. Burgess, Y. Riffo-Vasquez; Sackler Institute of Pulmonary Pharmacology, King’s College London, London, United Kingdom, Immune Regulation Ltd. Stevenage, United Kingdom.

Abstract
Introduction: Epidemiological data suggests that M. tuberculosis (mTB) infection prevents asthma development. Chaperonin 60.1 (Cpn60.1), a protein secreted by mTB to dampen down the host immune response while in a latent state in the lung, inhibits allergic pulmonary inflammation and bronchial hyperresponsiveness in a murine model (Riffo-Vasquez, Y et al. AJRCMB, 47(2):245, 2012). We have investigated the effect of PIN201104, a synthetic, low molecular weight, short PK half-life (blood T1/2, 10min after i.v administration) molecule derived from Cpn60.1 in murine models of allergic lung inflammation. Methods: OVA model: Mice were sensitised with ovalbumin (OVA) and from day 14 were challenged with OVA (3%) once daily for 3 days. PIN201104 (20 ng/kg, i.v.) was given either, 5 min before each sensitization (G1), or before each OVA challenge (G2). Bronchoalveolar lavage (BAL) was performed at 24 h after the third OVA challenge or 10 days later upon re-challenge, when no further treatment with PIN201104 was given. HDM model: Mice were sensitised with house dust mite (HDM 25μg) intra-nasally for three weeks. Two weeks after the final sensitization animals were challenged with HDM (i.n. 100μg). PIN201104 (2μg/kg i.n.) or controls were administered prior to HDM challenge. Fourteen days later, mice were re-challenged with HDM and BAL samples were taken. Results: OVA model: PIN201104 markedly inhibited eosinophil recruitment to the lung 24h after challenge, when given either during sensitisation or before each challenge, (OVA: 42.7 ± 12.4 vs PIN201104 G1: 7.8 + 2.2, PIN201104 G2: 13.7 + 6.1 x 10 /ml, (P<0.05), and also when re-challenged 10 days after the 3 PIN21104 treatment (OVA: 18.4 ± 12.4 vs PIN201104 G1: 5.7 + 1.1, PIN201104 G2: 6.4 + 3 x 10 /ml, P<0.001) HDM model: 4hrs after re-challenge, PIN201104 (i.n.) markedly reduced BAL eosinophils (84±5%), neutrophils (67±4%) and lymphocytes (52±12%), 14 days after a single administration (P<0.05). Moreover, it also reduced levels of Th-2 cytokines (IL-4, IL-5, IL-13) in the BAL at the same time point. In contrast, fluticasone, montelukast or anti-IL-5 (other than reduced eosinophils) had no significant effect at this time point Conclusion: PIN201104 significantly inhibits the recruitment of inflammatory cells to the lung in two models of allergic inflammation. The very short exposure time of PIN201104, the prolonged nature of inhibition of cell recruitment, and the reduction in Th-2 cytokines, suggests that its effects are novel, and likely to be through a resetting of immune homeostasis. Thanks to GSK for performing the HDM model.

Enquiries
Immune Regulation
Richard Nagle, CEO
+44 (0)7809 525267
info@immuneregulation.com

Instinctif Partners
Melanie Toyne-Sewell / Rozi Morris
+44 (0)20 7457 2020

About Immune Regulation Limited
Immune Regulation is a clinical stage biotech company, pioneering new technologies for resetting the immune system, developing novel, first-in-class therapies for inflammatory and immunological diseases. These therapies reset the immune system from a pro-inflammatory to a regulatory state to induce long-term disease remission in patients with allergic and immune mediated diseases, without the negative effects of chronic current therapies.

Lead drug candidates, IRL201805 (‘1805) and IRL201104 (‘1104) have successfully completed Phase 1/2a and Phase 1 studies, respectively. Both molecules have demonstrated a durable regulation of the immune system for a significant time period after a single dose and both appear to have very clean safety profiles. They appear to modulate key cells of the immune system that control the inflammatory response, with a long duration of action following a single dose (‘1805, up to 12 weeks; ‘1104, up to 14 days) despite their short pharmacokinetic half-lives. Furthermore, despite regulating the immune system they do not appear to suppress host defence, having shown no impact to date on the body’s ability to fight infection. Rather, they are immunomodulators: they appear to reset the immune response with the potential for inducing long-term disease remission.

22 May 2019