INV103 (ala-Cpn10)

INV103 (ala-Cpn10) – replicating a naturally occurring human protein for the treatment of chronic inflammation  

Chaperonin 10 is a naturally occurring protein present in all cells that, in conjunction with chaperonin 60, performs the essential housekeeping role of protein folding, i.e. it helps proteins develop into exactly the right shape required for  them to work effectively. Chaperonin 10 is thought to function as a natural regulator of the innate immune system: it is released locally by activated or damaged cells in response to “danger” signals, and down-regulates inflammatory immune responses. It is hypothesized that in disease states, levels of chaperonin 10 may not be high enough to control inflammation; however, administration of pharmacological levels of chaperonin 10 may overcome ongoing inflammatory signals and result in therapeutic benefit.

Invion’s asset, INV103 (ala-Cpn10), is a minimally modified version of the naturally occurring chaperonin 10, and, in clinical trials conducted to date, has been demonstrated to also have an immunomodulatory function. Mirroring its endogenous counterpart, ala-Cpn10 appears to work in a way which distinguishes it from current registered therapies for the treatment of inflammatory diseases including rheumatoid arthritis and lupus – by down-regulating rather than ablating excessive inflammatory responses, ala-Cpn10 shows the potential to restore a balanced immune response.

On 17 August 2015, the Company announced it had completed its phase II clinical trial entitled of INV103 (ala-Cpn10) in lupus patients. Three sets of data were reviewed from subjects who received twice-weekly doses of 10, 30 or 100mg of ala-Cpn10, or placebo. The adverse events and clinical chemistry profiles showed that increasing the dose 10-fold over levels used previously in the development of the drug asset could be achieved safely. Serum biomarkers of vascular inflammation were too variable in all cohorts to draw absolute conclusions about biological effect. However significant data were derived from extracting white blood cells from patients before and after certain doses and stimulating these cells (peripheral blood monocytic cells or PBMCs) to produce inflammatory signals.  PBMCs are hypothesized to play a critical role in autoimmune diseases.

Subjects in the first cohort, who received 10mg intravenously twice-weekly for four weeks, showed no consistent effect on stimulated PBMC production of 3 key cytokines (IL-1Beta, IL-6 and TNF-alpha) measured at two time points. In contrast, subjects in the second cohort (30mg intravenously twice-weekly for four weeks) showed a consistent decrease in production of all three cytokines measured at the same two time points in stimulated PBMC.  Data from the third cohort (100mg intravenously twice-weekly for four weeks) support findings from the second cohort, although, like the placebo data, had some variability.

INV103 (ala-Cpn10) will need scale-up and longer term toxicology to extend these findings from one month to longer term studies in larger groups of subjects. The Company is providing these data to potential partners in the near term, with a view to partnering the program.