22 December 2022 - - Taiwan-based clinical-stage biopharmaceutical company Regimmune Ltd announced the positive results of their Phase 2b clinical trial for the prevention of acute graft-versus-host disease (aGvHD) after allogeneic hematopoietic cell transplantation at the 2022 American Society of Hematology annual meeting, the company said.

RGI-2001 activates Regulatory T-cells (Tregs) through a novel mechanism that may have implications for the treatment of other autoimmune and chronic inflammatory diseases.

Patients who undergo HCT have a high-risk of developing aGVHD which is associated with significant morbidity and mortality.

Acute GVHD is characterized as a reaction of donor immune cells against host tissues.

Despite the use of prophylactic immunosuppressive therapy, clinically significant aGvHD develops in 20%-40% of matched related and unrelated allogenic HCT and severe cases contribute to non-relapse mortality.

RGI-2001, added to standard immunosuppression, is being evaluated for the potential to reduce or prevent aGvHD after HCT.

Earlier studies had shown that a single dose of RGI-2001 given on the day of transplantation was safe and potentially contributed to aGvHD prevention.

This phase 2b clinical trial was an open-label, multi-center, single-arm study to evaluate six weekly doses of RGI-2001 in combination with standard of care tacrolimus/methotrexate for the prevention of aGvHD in patients following allogenic HCT.

RGI-2001 was administered at a dose of 100 ug/kg IV infusion weekly for 6 weeks, starting on the day of transplantation.

The study included 49 patients and was conducted in the US at 7 centers.

Efficacy Results from the phase 2b trial in allogenic HSCT patients:

All 49 patients had at least 100 days of follow-up after HCT, and 39 of 49 had complete follow-up to day 180. The median follow-up of survivors was 310 days (range 111-365 days)

There were no cases of engraftment failure and no serious adverse events attributed to RGI-2001; and treatment emergent adverse events include gastrointestinal AE such as diarrhea, stomatitis and nausea.

Through day 100, the incidence of grades II-IV aGvHD was 20.4% (95% confidence interval 10.2-34.3%), only 2 cases of which were grades III-IV aGvHD [(4.1% (0.5-14.0%)).

At day 180, estimates of overall survival, grades II-IV aGvHD-free survival, and disease relapse were 93.6% (81.6-97.9%), 75.2% (60.5-85.1%), and 4.1% (0.7-12.6%), respectively.

Regimmune concludes that intravenous administration of RGI-2001 added to standard-of-care tacrolimus/methotrexate showed promising efficacy in the prevention of clinically significant aGvHD with a favorable safety profile. Based on these compelling phase 2b results, Regimmune is strongly considering moving forward with a phase 3 study.

RGI-2001 is a liposomal formulation of an alpha-galactosylceramide (alpha-GalCer) analog. Alpha-GalCer is a ligand for CD1d expressed on antigen presenting cells and invariant natural killer T cells.

Liposomal alpha-GalCer promotes tolerogenic immune cascades, resulting in the activation and expansion of regulatory T cells (Tregs).

RGI-2001 is Regimmune's lead drug candidate currently in Phase 3 planning for the prophylaxis of acute graft-versus-host disease (aGVHD).

Regimmune is a clinical-stage biopharmaceutical company focused on creating innovative immunotherapies by harnessing the power of regulatory T cells (Tregs).

Regimmune is creating a pipeline of novel product candidates that either enhance Treg activities for immune diseases or suppress Treg activities for cancer.