EMMUNE, INC. - Florida Company Profile

462445960

2021

7

5612957284

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2020

7

5612957284

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2022-12-22

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Department of Health and Human Services

PROCESS DEVELOPMENT FOR MANUFACTURING ECD4-IG - ABSTRACT ECD4-IG IS AN ANTIBODY-LIKE THERAPEUTIC FOR HIV THAT WAS CONSTRUCTED BY FUSING CD4 DOMAINS 1 AND 2, AND AN HIV CORECEPTOR-MIMETIC SULFOPEPTIDE, TO THE N- AND C-TERMINI OF THE CONSTANT FC REGION OF AN ANTIBODY. ECD4-IG WILL JOIN AN EMERGING CLASS OF LONG-ACTING THERAPEUTICS FOR TREATING AND PREVENTING HIV INFECTION. AS A CONSEQUENCE OF BEING BUILT FROM PARTS OF HIV’S RECEPTORS, ECD4-IG NEUTRALIZES 100% OF HIV ISOLATES, AND EVEN NEUTRALIZES SIMIAN IMMUNODEFICIENCY VIRUS (SIV). THUS, ECD4-IG PRESENTS FUNDAMENTAL BARRIERS TO ESCAPE. THIS GRANT WILL FUND THE WORK THAT IS NEEDED IN BETWEEN CELL LINE DEVELOPMENT AND IND-ENABLING STUDIES TO BRING ECD4-IG TO THE CLINIC. IN PHASE I, WE WILL VALIDATE ASSAYS FOR CRITICAL QUALITY ATTRIBUTES (CQAS) INCLUDING THE SULFOTYROSINE CONTENT OF THE CORECEPTOR-MIMETIC SULFOPEPTIDE, AND THEN SHOW THAT THE ECD4-IG PROTEIN MADE BY NEW CELL LINES MEETS PRE-DEFINED CQAS. IN PHASE II, WE WILL OPTIMIZE OUR UPSTREAM PROCESS, DOWNSTREAM PROCESS, FORMULATION BUFFERS, AND GENERATE A GLP LOT OF ECD4-IG PROTEIN FOR IND-ENABLING STUDIES. FEATURES OF THE UPSTREAM PROCESS THAT WILL BE OPTIMIZED INCLUDE MEDIA AND FEED SELECTION, A TEMPERATURE SHIFT, AND FED-BATCH VERSUS PERFUSION CULTURE. OUR DOWNSTREAM PROCESS IS BASED ON CONVECTIVE CHROMATOGRAPHY, INCLUDING FOR PROTEIN A AFFINITY CHROMATOGRAPHY, ANION EXCHANGE (AEX) CHROMATOGRAPHY, AND HYDROPHOBIC INTERACTION (HIC) CHROMATOGRAPHY. THESE PROCESSES EFFICIENTLY REMOVE POORLY SULFATED ECD4-IG, AGGREGATES, AND HOST CELL PROTEIN (HCP). WE WILL DEVELOP A FORMULATION FOR INTRAVENOUS INJECTION, AND A HIGH-CONCENTRATION FORMULATION WITH ACCEPTABLE VISCOSITY FOR SUBCUTANEOUS INJECTION. PRODUCTION OF A GLP LOT OF PROTEIN FOR IND-ENABLING STUDIES WILL BE OUTSOURCED TO A CMO AFTER A TECHNOLOGY TRANSFER PROCESS. THESE ARE THE ESSENTIAL NEXT STEPS TOWARDS BRINGING ECD4-IG TO THE CLINIC.

299998.00

0.00

0.00

2022-08-11

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Department of Health and Human Services

SARS-COV-2 VACCINES BASED ON RBDS WITH ENGINEERED GLYCOSYLATION SITES - ABSTRACT WE ARE DEVELOPING VACCINE ANTIGENS FOR SARS-COV-2 THAT FOCUS THE ANTIBODY RESPONSE ONTO NEUTRALIZING EPITOPES IN THE RECEPTOR BINDING DOMAIN (RBD) OF THE VIRAL SPIKE (S) PROTEIN. EFFICIENT EXPRESSION OF THE RBD IN TECHNICALLY-DEMANDING FORMATS, E.G., ON A SELF-ASSEMBLING MULTIMER SCAFFOLD, WAS ACHIEVED BY ENGINEERING N-LINKED GLYCOSYLATION SITES INTO THE RBD. THE ENGINEERED N-LINKED GLYCOSYLATION SITES OCCLUDE HYDROPHOBIC PATCHES THAT FORM INTER-SUBUNIT INTERFACES IN THE NATIVE S PROTEIN, BUT THAT INTERFERE WITH EXPRESSION OF THE RBD IN OTHER CONTEXTS. THE GLYCANS ALSO HELP TO FOCUS THE IMMUNE RESPONSE AWAY FROM OFF-TARGET FACES OF THE RBD, AND ONTO THE TARGETS FOR POTENT NEUTRALIZING ANTIBODY RESPONSES. WE WILL EXTEND THE POTENTIAL FOR THIS STRATEGY TO FOCUS THE NEUTRALIZING ANTIBODY RESPONSE FURTHER, ONTO CONSERVED EPITOPES IN THE RBD. THIS OVERALL STRATEGY MAXIMIZES THE FOCUSING OF NEUTRALIZING ANTIBODY RESPONSES ONTO EPITOPES THAT ARE CONSERVED AMONG VARIANTS OF SARS-COV-2. IN ADDITION, WE WILL COMPARE, AND POSSIBLY COMBINE, IMMUNOFOCUSING WITH APPROACHES DESIGNED TO ELICIT VARIANT-SPECIFIC NEUTRALIZING ANTIBODIES. WE WILL DEVELOP AND UTILIZE TWO DISTINCT PLATFORMS FOR EXPRESSING THESE RBD ANTIGENS: MRNA DELIVERED BY LIPID NANOPARTICLES (LNPS), AND A NOVEL SCAFFOLD FOR EFFICIENTLY DISPLAYING MULTIMERS OF RBD ANTIGENS AS RECOMBINANT PROTEIN. LNP-MRNA VACCINES HAVE THE ADVANTAGE OF BEING A VALIDATED APPROACH FOR VACCINATING AGAINST SARS-COV-2, WHEREAS THE NOVEL MULTIMER SCAFFOLD HAS THE ADVANTAGE OF BEING HEAT STABLE AFTER LYOPHILIZATION. THE ANTIGENS GENERATED BY THIS PROJECT EXPLOIT THREE LAYERS OF IMMUNOFOCUSING TO ELICIT OR BOOST ANTIBODY RESPONSES THAT NEUTRALIZE DIVERSE VARIANTS OF SARS-COV-2.

2300000.00

0.00

0.00

2021-07-13

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Department of Health and Human Services

GLYCOENGINEERING ECD4-IG - ABSTRACT WE ARE DEVELOPING ECD4-IG, AN ANTIBODY-LIKE MOLECULE CONSTRUCTED FROM CD4, A CORECEPTOR-MIMETIC PEPTIDE, AND AN ANTIBODY FC, AS A LONG-ACTING INJECTABLE THERAPEUTIC FOR HIV. OUR PROGRESS TO-DATE INCLUDES HAVING EXTENDED THE PLASMA HALF-LIFE OF ECD4-IG TO THE POINT THAT IT NOW RIVALS OR SURPASSES THAT OF THE LEADING BROADLY NEUTRALIZING ANTIBODIES (BNABS) BEING DEVELOPED AS LONG-ACTING INJECTABLES. IN A HEAD-TO-HEAD COMPARISON OF PHARMACOKINETICS (PK) IN THE HUMAN FCRN-TRANSGENIC MOUSE MODEL, ECD4-IG HAD SIGNIFICANTLY BETTER PK THAN A VRC01 PROTEIN THAT HAD A HALF-LIFE OF 71 DAYS IN HUMANS (GAUDINSKI ET AL., PLOS MED, 2018). WITH SUPPORT FROM NIAID, WE HAVE DEVELOPED A CHO CELL LINE FOR MANUFACTURING ECD4-IG UNDER CGMP CONDITIONS. HOWEVER, IN-DEPTH ANALYSIS OF THE COMPOSITION OF THE N-LINKED GLYCANS (NLGS) AT N297 OF THE FC OF THE PROTEIN MADE BY THE CELL LINE HAS HIGHLIGHTED A PROBLEM SHARED BY THE ENTIRE FIELD: THE LARGE MAJORITY OF THE NLGS ARE FORMS DETRIMENTAL TO PK. THIS PROBLEM IS PARTICULARLY PRONOUNCED AMONG THE AFUCOSYLATED FORMS THAT ARE ACTIVE FOR ANTIBODY- DEPENDENT CELL-MEDIATED CYTOTOXICITY (ADCC). INDEED, ONLY A FEW PERCENT OF THE NLGS ARE AFUCOSYLATED FORMS THAT ALLOW BOTH ADCC AND A LONG HALF-LIFE. THEREFORE, WE PROPOSE GLYCOENGINEERING OUR CELL LINE FOR MANUFACTURING ECD4-IG. TO DO SO, WE WILL DEVELOP A GLYCOENGINEERING GENE CASSETTE, INTRODUCE IT INTO THE CELL LINE, AND DERIVE A GLYCOENGINEERED CLONE FOR MANUFACTURING ECD4-IG UNDER CGMP CONDITIONS. ALTHOUGH OUR PRIMARY GOAL IS TO MANUFACTURE ECD4-IG PROTEIN CONSISTING ALMOST ENTIRELY OF A SINGLE LONG-LIVED GLYCOFORM THAT IS ACTIVE FOR ADCC, THE SAME GLYCOENGINEERING GENE CASSETTE CAN BE USED TO MANUFACTURE OTHER ANTIBODY THERAPEUTICS, INCLUDING BNABS, TO SIMILARLY EXTEND EFFECTOR FUNCTION AND PLASMA HALF-LIFE. THIS WORK WILL REDUCE THE THERAPEUTIC CONCENTRATION AND INCREASE THE INTERVAL AT WHICH LONG-ACTING PROTEIN THERAPEUTICS FOR TREATING AND PREVENTING HIV INFECTION CAN BE DOSED.

3249324.00

0.00

0.00

2020-08-18

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Department of Health and Human Services

ENGINEERING AAV CAPSIDS FOR ENHANCED TRANSDUCTION OF SKELETAL MUSCLE

2349344.00

0.00

0.00

2020-04-14

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Small Business Administration

TO AID SMALL BUSINESSES IN MAINTAINING WORK FORCE DURING COVID-19 PANDEMIC.

0.00

141895.00

141895.00

2020-04-14

Paid in Full

100

141895

141895

Unanswered

Unknown/NotStated

Unanswered

Non-Veteran

142714.84