Targeting leukocyte metabolism to treat human autoimmune disease

ImmuNext has defined an anti MCTmonoclonal antibodymAbthat will be developed for the treatment of human autoimmune diseaseThe membrane monocarboxylate nutrient transporter SLCAMCTis a multi pass transmembrane protein responsible for the facilitated transport of critical metabolitesincluding products of glycolysislactatepyruvate and ketonesOur strong preliminary data support the tenet that mAbs that block MCTtransport of monocarboxylatesincluding lactatefrom activated lymphocytes will attenuate key inflammatory effector functionsthereby suppressing immune function and safely treat human autoimmune diseasesWe show the unique advantage of mab approaches over that of small molecules that are toxic and lack transporter specificityThe mechanism of MCTinhibition to reduce proliferation and cytokine production from lymphoidbut not myeloid cells is a unique approach and data suggest that its modulation is best suited for SLE treatmentwhere nontoxic drugs that target both T and B cells are lackingWith a strong patent positionstate of the art approaches and a skilledexperienced drug development teama first in classtherapeutic mab that selectively ablates lymphoid metabolism for the treatment of autoimmune disease will be developedIn Phasewe will humanize the rat anti MCTantibody and select mab leads for PhaseWe currently have both a human CDCDactivated T cell assay for our primary screen and a secondary MCTtoxin transport assay for lead antibody selectionOur choice of the lead therapeutic antibody will be determined fromICdeterminations using in vitro lymphocyte assays andby quantifying the in vivo potency in a xeno GVHD modelhuman PBMCNSG miceAfter selection of the lead antibody and a backupwe will advance into Phasewith lead optimization and pre clinical developmentThe lead will be assessed for immunogenicity and manufacturing propertiesPK will be determined and we will expand upon our existing ketone PD biomarkers to inform future clinical plans using a variety of approachesincluding metabolomicscytokine analysis and RNA seqBy examining the mechanism of action using human SLE patient samples compared to healthy controls and using established transport and immunological assayswe will identify additional biomarkers for patient stratification in the planned clinical trialsWith a qualified lead in handwe will commence cell line development and non GLP PK PD toxicological studies in cynomolgus non human primatesWe have convened a panel of experts that will help collectanalyze and process the data generated from these studies to assist in outlining an IND enabling GLP tox study and a clinical strategy going forwardOur first in class anti MCTmAb will ultimately provide patients with a unique immunometabolic targeting drug that will not only treat their symptomsbut also abrogate ongoing disease and synergize with existing therapies to provide long term remission and cure MCTis an important metabolite transporter expressed on the white blood cellsthese cells being one of the main components in autoimmune disease developmentImmuNext has developed a novel antibody that binds and blocks the function of MCTleading to the suppression of the overactive immune system and potential disease regressionThrough a series of engineeringscreening and optimization stepswe plan to develop this antibody into a novel drug that can provide lupus patients with a therapy that will reset their diseased immune systemrestoring them to a healthybalanced state