Targeting the checkpoint regulator VISTA for treatment of inflammatory disease

ImmuNext has identified and developed a putative lead anti VISTA monoclonal antibody mAb that we aim to bring to the clinic for the treatment of human autoimmune disease VISTA is a member of the highly successful negative checkpoint regulator NCR family of drug targets whose members have demonstrated proven efficacy in inducing long term remissions in human cancers We contend that antibodies that suppress immune function by enhancing VISTAandapos s function will prove effective in a broad array of human autoimmune diseases The unique nature of VISTA to regulate both lymphoid and myeloid cells suggests that its modulation will be best suited toward the treatment of SLE where defects in both subsets have been identified With a strong patent position state of the art approaches and a skilled experienced drug development team we will develop a first in class NCR targeted therapeutic for the treatment of autoimmune disease In Phase we will identify a cynomolgus cross reactive lead and a backup mAb through functional screening of an anti VISTA human antibody library We currently have a human CD activated T call assay for our primary screen Our choice of the best functional antibody and a backup will come from using in vitro assays by confirming activity using a human VISTA knock in hV KI mouse strain and with two models of autoimmune inflammation concanavalin A induced hepatitis and following selection a graft vs host disease model After selection of the best antibody and a backup we will advance into Phase with lead optimization and pre clinical development The constant region of the lead antibody will be engineered through Ig isotype and FcRn engineering and we will choose the best one to develop as the final lead molecule This lead will be assessed for immunogenicity and manufacturing liabilities and will be used to study the mechanism of action MOA in hV KI mice Additionally we will examine the potential for this new therapeutic to induce immunological tolerance using transplant models PK PD relationships will be measured and rodent toxicity investigated We will also develop PD biomarkers to inform future clinical plans using a variety of approaches including examining tissues and cells by Phosflow and RNA seq in drug treated settings By examining VISTA and the lead MOA in SLE human patient samples compared to healthy controls we will potentially identify VISTA biomarkers for future clinical trials With a qualified lead in hand we will commence cell line development and non GLP PK PD and toxicological assessment in cynomolgus non human primates We have convened a panel of experts that will help collect analyze and process the data generated from these studies to outline a clinical strategy and an IND enabling GLP tox study The first in class anti VISTA mAb will ultimately provide patients with a unique checkpoint regulator drug to not only treat their symptoms but also to provide them the opportunity to reset their immune system back to a healthy homeostatic state VISTA is an immune regulatory protein expressed on certain white blood cells that plays a key role in switching off the immune system ImmuNext Inc has developed a novel human antibody that binds to VISTA leading to the suppression of an overactive immune system Through a series of engineering screening and optimization steps we plan to develop this antibody into a novel drug therapy that would help patients with lupus reset their overactive immune system and restore them to a healthy state