IMMUNEXT PHARMACEUTICALS — Department of Health and Human Services SBIR Phase II: R

Description

ImmuNext has identified and developed a putative lead anti VISTA monoclonal antibodymAbthat we aim to bring to the clinic for the treatment of human autoimmune diseaseVISTA is a member of the highly successful negative checkpoint regulatorNCRfamily of drug targetswhose members have demonstrated proven efficacy in inducing long term remissions in human cancersWe contend that antibodies that suppress immune function by enhancing VISTA s function will prove effective in a broad array of human autoimmune diseasesThe unique nature of VISTA to regulate both lymphoid and myeloid cells suggests that its modulation will be best suited toward the treatment of SLEwhere defects in both subsets have been identifiedWith a strong patent positionstate of the art approaches and a skilledexperienced drug development teamwe will develop a first in class NCR targeted therapeutic for the treatment of autoimmune diseaseIn Phasewe will identify a cynomolgus cross reactive lead and a backup mAb through functional screening of an anti VISTA human antibody libraryWe currently have a human CDactivated T call assay for our primary screenOur choice of the best functional antibody and a backup will come fromusing in vitro assaysby confirming activity using a human VISTA knock inhV KImouse strain andwith two models of autoimmune inflammationconcanavalin A induced hepatitis andfollowing selectiona graft vshost disease modelAfter selection of the best antibody and a backupwe will advance into Phasewith lead optimization and preclinical developmentThe constant region of the lead antibody will be engineered through Ig isotype and FcRn engineeringand we will choose the best one to develop as the final lead moleculeThis lead will be assessed for immunogenicity and manufacturing liabilitiesand will be used to study the mechanism of actionMOAin hV KI miceAdditionallywe will examine the potential for this new therapeutic to induce immunological tolerance using transplant modelsPK PD relationships will be measured and rodent toxicity investigatedWe will also develop PD biomarkers to inform future clinical plans using a variety of approachesincluding examining tissues and cells by Phosflow and RNA seq in drug treated settingsBy examining VISTA and the lead MOA in SLE human patient samples compared to healthy controlswe will potentially identify VISTA biomarkers for future clinical trialsWith a qualified lead in handwe will commence cell line development and non GLP PK PD and toxicological assessment in cynomolgus non human primatesWe have convened a panel of experts that will help collectanalyze and process the data generated from these studies to outline a clinical strategy and an IND enabling GLP tox studyThe first in class anti VISTA mAb will ultimately provide patients with a unique checkpoint regulator drug to not only treat their symptomsbut 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 systemImmuNextInchas developed a novel human antibody that binds to VISTAleading to the suppression of an overactive immune systemThrough a series of engineeringscreening and optimization stepswe 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