RGI-2001 is a liposomal formulation of KRN7000, an alpha-galactosylceramide analog, embedded within the lipid bilayer to promote uptake by antigen presenting cells and presentation by CD1d. In animal models, invariant NKT cells promoted the activation and expansion of Treg, leading to suppression of alloreactive donor T cells in graft-versus-host disease (GVHD) models. Based on these animal studies, a phase I/IIa open label, multicenter, dose escalation study of a single dose RGI-2001 was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of RGI-2001 in allogeneic hematopoietic cell transplant (HCT) patients. Results of this study showed that RGI-2001 was well-tolerated and that some patients treated with RGI-2001 had markedly increased numbers of Treg (CD4+CD25+CD127lowFoxp3+) within 1–3 weeks after HCT. The patients who responded with an increased number of Treg also had decreased GVHD compared to non-responders. A phase II multicenter, multiple dosing RGI-2001 has been initiated and is currently recruiting patients.
RGI-Ab01. Our lead Treg inhibition therapeutic antibody, RGI-Ab01, is a potent, high affinity-binding antibody to a target specifically expressed on Tregs in the tumor microenvironment. RGI-Ab01 is designed specifically for the biology of the tumor microenvironment and has multiple advantages over other Treg targeted molecules in clinical development, including: (i) significantly greater potency under conditions that closely resemble the tumor microenvironment, for example, high target expression on tumor-derived Tregs, (ii) high penetration of tumor tissue, (iii) attractive pharmacokinetics, and (iv) low toxicities with no systemic depletion of Tregs. RGI-Ab01 is currently in late discovery.
RGI-Ab02. A novel checkpoint inhibitor therapeutic antibody, RGI-Ab02, binds to an inhibitory receptor expressed on CD8+ Effector T cells and NK cells. We believe that RGI-Ab02 will have efficacy as a monotherapy and also in combination with anti-PD-1 therapies as well as our internal antibody therapeutic products. RGI-Ab02 is currently in early discovery.