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Principal Investigator: Jean-Loup Romet-Lemonne
Organization: TRAVERSE BIOTECH II INC
Fiscal Year: 2024
Award: $298,938
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
We are developing the first orally available immunotherapy product, HPX-612, for the treatment of visceral
leishmaniasis, a parasitic disease caused by Leishmania and transmitted by sandflies. Visceral leishmaniasis
remains endemic in 65 countries worldwide, with over 4 million people impacted globally. Current treatment
options require lengthy and painful injections and have significant limitations including low therapeutic index,
severe side effects, acute cytotoxicity, high associated hospital costs and emergence of their resistance strains.
Additionally, these treatments are often inaccessible to those living in the remote areas where Leishmania is
prevalent. Leishmania infection is heavily dependent on host monocytes and macrophages as once the parasite
enters the human body, it is engulfed by monocytes and macrophages where it inhibits macrophage activation
and replicates. Recent studies have identified the nucleotide-binding oligomerization domain-containing protein
2 (NOD2) as a critical regulator in the intracellular killing of Leishmania parasites. Further, NOD2 agonism in
infected monocytes and macrophages provide a novel host-targeted therapeutic strategy that increases
immunosurveillance via activation of the innate immune system that resolves leishmaniasis.
HPX-612 is a novel lipid nanoparticle and potent innate immune stimulator that is comprised of the active
pharmaceutical ingredient muramyl tripeptide phosphatidylethanolamine (MTP-PE), a NOD2 agonist with
demonstrated clinical safety. MTP-PE is the active pharmaceutical ingredient in the EMA-approved intravenously
delivered MepactÒ for non-metastatic osteosarcoma. HPX-612 has a demonstrated capacity to cross the gut-
blood barrier creating a sustained NOD2 stimulation and potent pro-inflammatory conversion of monocytes and
macrophages after oral dosing. When approved, HPX-612 will be delivered external to hospital settings and over
longer time periods to efficiently combat visceral leishmaniasis in regions that need it most. Herein this
application we will evaluate the preclinical pharmacokinetic profile of HPX-612, optimal posology, and
confirmation of efficacy in a murine model of visceral leishmaniasis. These results will support the launch of
HPX-612 into full-scale preclinical development for the treatment of leishmaniasis and a future Phase II
application.
Terms: <2-Aminoethanol><Acute><Affect><Agonist><AmB><AmBisome><Aminoethanols><Aminosidine><Amphocil><Amphotec><Amphotercin B><Amphotericin><Amphotericin B><Area><BALB C Mouse><BALB/c><Binding><Biotech><Biotechnology><Blood><Blood Reticuloendothelial System><Blood granulocytic cell><Blood monocyte><Bone Sarcoma><Catenulin><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cephalins><Clinical><Colamine><Collaborations><Communities><Country><Cutaneous Leishmaniasis><Disease><Disorder><Dose><Drug Kinetics><Drug usage><Estomycin><Ethanolamine Phosphoglycerides><Ethanolamineglycerophospholipids><Ethanolamines><Europe><Formulation><Fungizone><Future><Gene variant><Genetic study><Granular Leukocytes><Granulocytic cell><Hepatic Failure><Hospital Admission><Hospital Costs><Hospitalization><Hospitalization cost><Hospitals><Human><Human Figure><Human body><Hydroxymycin><Immune><Immune Surveillance><Immune mediated therapy><Immunes><Immunologic Surveillance><Immunologic Surveillances><Immunological Surveillance><Immunological Surveillances><Immunologically Directed Therapy><Immunostimulatory drug><Immunosurveillance><Immunotherapy><In Vitro><Inbred BALB C Mice><Individual><Infection><Inflammatory><Injections><Innate Immune System><Intracellular Communication and Signaling><Intravenous><Kala-Azar><Kidney Failure><Kidney Insufficiency><Kinetics><L donovani><L. donovani><LMIC><Laboratories><Left><Leishmania><Leishmania (Leishmania) donovani><Leishmania donovani><Leishmaniasis><Liposomal><Liposomes><Liver Failure><Low-resource area><Low-resource community><Low-resource environment><Low-resource region><Low-resource setting><Lytotoxicity><Macrophage><Macrophage Activation><Marketing><Marrow monocyte><Mice><Mice Mammals><Miltefosin><Miltefosina><Miltefosine><Miltefosinum><Modern Man><Molecular Interaction><Monitor><Monoethanolamine><Morbidity><Morbidity - disease rate><Murein><Murine><Mus><Mysteclin-F><Mφ><Names><Neomycin E><New York><Non-metastatic><Nonmetastatic><Nucleotides><O-(1-beta-acyl-2-acyl-sn-glycero-3-phospho)-ethanolamine><Oral><Oral Administration><Oral Drug Administration><Osseous Sarcoma><Osteogenic Sarcoma><Osteosarcoma><Pain><Painful><Paramomycin><Parasites><Parasitic Diseases><Parasitology><Paromomycin><Pathogenicity><Pathway interactions><Pattern recognition receptor><Peptides><Peptidoglycan><Persons><Phagocytes><Phagocytic Cell><Pharmaceutical Agent><Pharmaceuticals><Pharmacokinetics><Pharmacologic Substance><Pharmacological Substance><Phase><Phlebotominae><Phosphatidylethanolamine><Predisposition><Principal Investigator><Program Development><Proteins><Renal Failure><Renal Insufficiency><Resource-constrained area><Resource-constrained community><Resource-constrained environment><Resource-constrained region><Resource-constrained setting><Resource-limited area><Resource-limited community><Resource-limited environment><Resource-limited region><Resource-limited setting><Resource-poor area><Resource-poor community><Resource-poor environment><Resource-poor region><Resource-poor setting><Safety><Signal Transduction><Signal Transduction Systems><Signaling><Skeletal Sarcoma><Susceptibility><Symbiosis><Therapeutic><Therapeutic Effect><Therapeutic Index><Time><Toxic effect><Toxicities><Transmission><Treatment Period><Underserved Population><Universities><Vector-borne disease><Vector-borne infectious disease><Vector-transmitted disease><Vector-transmitted infectious disease><Visceral><Visceral Leishmaniasis><Work><allele variant><allelic variant><amebocyte><assay development><biological signal transduction><combat><commensalism><cytotoxicity><dermal leishmaniasis><determine efficacy><develop therapy><drug candidate><drug use><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><experience><experiment><experimental research><experimental study><experiments><genetic variant><genomic variant><granulocyte><immune stimulatory agent><immune stimulatory drug><immune stimulatory therapeutic><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><immunostimulatory agents><immunostimulatory biologics><improved><in vivo><intervention development><intraoral drug delivery><lipid based nanoparticle><lipid nanoparticle><low and middle-income countries><manufacturing quality><monocyte><mortality><mouse model><murine model><name><named><naming><neglected tropical diseases><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><osteochondrosarcoma><osteoid sarcoma><overexpress><overexpression><pathway><pharmaceutical><pharmacologic><pre-clinical><pre-clinical development><preclinical><preclinical development><quality assurance><resistance strain><resistant strain><response><sandfly><side effect><standard of care><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapy development><transmission process><treatment days><treatment development><treatment duration><under served group><under served individual><under served people><under served population><underserved group><underserved individual><underserved people><vector-borne illness><vectorborne disease><vectorborne illness><vectorborne infectious disease>