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Preclinical studies of PG70 LEAPS peptide vaccines for rheumatoid arthritis

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44AR063504-02A1
Agency Tracking Number: R44AR063504
Amount: $1,497,974.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIAMS
Solicitation Number: PA16-302
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-15
Award End Date (Contract End Date): 2019-08-31
Small Business Information
Vienna, VA 22182-2634
United States
DUNS: 102560141
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (703) 506-9460
Business Contact
Phone: (703) 506-9460
Research Institution

CurrentlyFDA licensed pharmaceuticals used to treat rheumatoid arthritisRAfocus largely on alleviation of
symptomseither through pain managementgeneral immunosuppressionor by antagonizing cytokines such as
TNFDespite recent advances in biologic therapiesthese treatments do not address the underlying
autoimmune conditionTo develop a peptide vaccine based therapy for RAwe used the human proteoglycanPGinduced arthritisPGIAand the closely related recombinant human PG Gdomain induced arthritisGIAmodels of RAtwo mouse models resembling the human disease in their pathologic and genetic featuresfemale
preponderanceproduction of anti citrullinated protein antibodies and rheumatoid factorThe ligand epitope antigen presentation systemLEAPSis a peptide vaccine platform designed to
modulate the immune response in an antigen specific mannerLEAPS peptides are composed of an immune cell
binding ligandICBLconjugated to a disease related peptideautoepitopeOne of the LEAPS conjugates is
CELwhich utilizes the DerG ICBL from the human MHC class IIchain that has T helper cellThpolarizing activitypotentially dampening Thor Thdriven autoimmune responses characteristic for RAIn the
phase I SBIR studywe showed that CELa DerG LEAPS conjugate of the immunodominant epitopePGof the Gdomain of the PG moleculeeffectively treats arthritis in the PGIA and GIA models of RAWe hypothesized and then demonstrated that the CELLEAPS vaccine modulates the underlying
immune responses that drive disease progression in PGIA and GIAEfficacy was demonstrated by suppressive
effects of CELon arthritis severityhistopathology of peripheral jointsand cytokine responsesThe four
Aims of the proposed phase II study areAimDetermine the in vitro T cell responses to CELthe antigen
presenting function of CELtreated dendritic cellsDCsand whether the conjugate alone and or
conjugate treated cells alter the differentiation of Thcells to distinct Th subsetsAimDemonstrate therapeutic
efficacy of LEAPS activated DCs or T cellsor a mixture of bothfrom mice with GIA after ex vivo treatment of
these cells with CELand adoptive transfer to immunodeficient miceAimExtend the CELbinding
and activation studies to ratnon human primateNHPand human peripheral blood cellsAimMeet with
FDA officialsreview the CELIND enabling program for in vivo immunogenicitytoxicity and safetyand
conduct the relevant and agreed upon in vivo vaccine treatment studies in NHPPerform IND enabling studies
using human cells and CELin a cytokine release assay as an independent assessment of a potential druginducedcytokine stormCompletion of these Aims will further elucidate the molecular basis for CELefficacy and lay the ground
work for an IND submissionThe proposed studies will further our understanding of the therapeutic immune
response elicited by LEAPS peptideand cell based vaccinesand initiate the steps towards human trials

* Information listed above is at the time of submission. *

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