Stevenage, UK—Immune Regulation announced today positive results from a Phase 1 study of its lead compound PIN201104 (‘1104). Immune Regulation, formerly known as Peptinnovate, is a biopharmaceutical company seeking to develop first in class immune-resetting therapies for asthma and other inflammatory diseases. PIN201104 has demonstrated immunoregulatory activity in a number of preclinical models. According to Immune Regulation, it has the potential to be the first Immune Resetting Asthma Drug (IMRAD).
“‘1104 is a low molecular weight peptide derived from chaperonin 60.1 with similar activities to the parent tuberculosis bacterium protein,” Immune Regulation’s website states. “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, ‘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 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 sensitized to be allergic to house dust mite, despite the compound being metabolized within a few hours (blood half-life, 10 minutes),” the website continues. “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.”
Study C1104-001 was a first in human, randomized, double blind, placebo controlled, parallel group study in healthy volunteers (HV) and patients with asthma to assess the safety, tolerability and pharmacokinetics of single ascending and repeat doses of ‘1104. The Phase 1 trial recruited 94 subjects including 16 mild asthmatics, and administered with ‘1104 either as a single ascending dose up to 8mg, repeat doses of 2mg on a single day or placebo, and then followed for 21 days.
The trial advanced through eleven cohorts of HV (44 active, 22 placebo) with a dose range of 0.02ng to 8mg, administered as a single IV bolus injection. Mild asthmatic patients received single IV doses of placebo, 2mg or 8mg (10 active, 6 placebo). Six HV (4 active, 2 placebo) received 2mg via subcutaneous injection. Six HV (4 active, 2 placebo) received 3x2mg doses two hours apart. The primary endpoints were safety and pharmacokinetic data.
The Phase 1 trial confirmed the clean safety profile of ‘1104 seen in pre-clinical studies, with the drug having a side effect profile comparable to placebo; the majority of events were classed as mild, and no serious or severe adverse events were reported. No dose limiting safety or tolerability was reported in the study, and no injection site reactions were seen in the small cohort of healthy subjects receiving subcutaneous dosing. Pharmacokinetic data from the trial showed exposure to ‘1104 was in-line with expectations based on pre-clinical work and was similar in both healthy volunteers and mild asthmatics. Based on these successful Phase 1 results Immune Regulation is moving forward with a Phase 2a proof of concept study, due to commence in the second half of 2019.
“These results for ‘1104 are a great validation of the safety of our immune-resetting platform,” said Richard Nagle, CEO of Immune Regulation. “It is exciting to now be embarking upon the next stage of development, and the data from this study will inform the preparations and protocols for our Phase 2a trial starting next year.”