Collins Industrial Blvd

NEURAL EXOSOME THERAPEUTICS FOR TREATING OPIOID-INDUCED BRAIN HYPOXIA INJURIES - 7. PROJECT SUMMARY/ABSTRACT NON-FATAL OPIOID-ASSOCIATED OVERDOSE (NFOO)-INDUCED BRAIN HYPOXIA AND INJURIES HAVE LIMITED TREATMENT OPTIONS. WHILE THE CURRENT THERAPEUTICS, SUCH AS NALOXONE, FOR FENTANYL OVERDOSES HAS SUBSTANTIALLY REDUCED FATALITIES, THE RESULTING BRAIN INJURIES FROM NFOO REMAIN A SIGNIFICANT CHALLENGE. NFOO-INDUCED BRAIN HYPOXIA WILL OFTEN RESULT IN NEUROINFLAMMATION AND NEURODEGENERATION, AND THERAPEUTICS THAT SUPPRESS THESE EFFECTS WILL PROVIDE A NEW OPPORTUNITY TO TREAT NFOO- INDUCED BRAIN INJURY. EXOSOMES ARE A NEW THERAPEUTIC STRATEGY THAT HAS RECENTLY EMERGED AS A TREATMENT FOR INFLAMMATORY DISEASES. EXOSOMES ARE A CLASS OF SMALL EXTRACELLULAR VESICLES CAPABLE OF DELIVERING VARIOUS CARGO (EG. PROTEINS/PEPTIDES, SIRNA, AND SMALL MOLECULES) TO CELLS FOR TREATMENT. SEVERAL CLINICAL TRIALS ARE UNDERWAY TO EVALUATE THE SAFETY AND EFFICACY OF EXOSOME THERAPEUTICS. THE MAJOR BENEFITS OF EXOSOME THERAPY ARE THEIR LOW IMMUNOGENICITY, ANTI-INFLAMMATORY ACTIVITY, ABILITY TO CROSS THE BBB AND TARGETING CAPABILITIES. ARUNA BIO HAS ESTABLISHED ITSELF AS A LEADER IN THE EXOSOME SPACE, DUE TO ITS PATENTED, NEURAL EXOSOME PLATFORM TECHNOLOGY. ARUNA’S NEURAL EXOSOMES, TERMED AB126, ARE GENERATED FROM HUMAN PLURIPOTENT STEM CELL-DERIVED NEURAL PROGENITORS AND HAVE AN ENHANCED ABILITY TO PENETRATE THE BBB TO TARGET NEURAL CELL TYPES. AB126, AS A STANDALONE THERAPEUTIC, HAS DEMONSTRATED EFFICACY FOR THE TREATMENT OF STROKE, THROUGH ITS NEUROPROTECTIVE AND ANTI-INFLAMMATORY EFFECTS, AND IS ANTICIPATED TO BE IN CLINICAL TRIALS DURING 2025. PRELIMINARY DATA IN THIS APPLICATION DEMONSTRATES AB126 ANTI- INFLAMMATORY EFFECTS, ALONG WITH OUR NOVEL PEPTIDE-EXOSOME COUPLING TECHNOLOGY THAT ENABLES ENDOSOME ESCAPE AND CAN BE EXTENDED FOR THERAPEUTIC PEPTIDE DELIVERY. AB126-COUPLED PEPTIDES POTENTIALLY REPRESENT A NEW CLASS OF THERAPEUTICS THAT COULD HAVE A MAJOR IMPACT FOR TREATING HYPOXIC BRAIN INJURIES. THE LONG-TERM GOAL OF ARUNA BIO IS TO DEVELOP NOVEL EXOSOME-BASED THERAPEUTICS FOR THE TREATMENT OF HYPOXIA- ASSOCIATED CNS DISEASES. IN THIS PHASE 1 PROPOSAL, AB126 WILL BE EVALUATED FOR ITS ABILITY TO SUPPRESS BRAIN HYPOXIA INDUCED NEUROINFLAMMATION FOLLOWING FENTANYL TREATMENT IN RATS (AIM 1), AND THE ABILITY OF AB126-COUPLED PEPTIDES, WHICH INHIBIT HYPOXIA SIGNALING, TO SUPPRESS FENTANYL EFFECTS IN VITRO AND IN VIVO (AIM 2). AT THE COMPLETION OF THIS STUDY, PROOF-OF-CONCEPT STUDIES FOR THE AB126 THERAPEUTICS FOR TREATING FENTANYL-INDUCED BRAIN INJURIES WILL HAVE BEEN DEMONSTRATED, WHICH WILL FACILITATE THE ADDITIONAL DEVELOPMENT OF AB126 THERAPEUTICS UNDER CHRONIC FENTANYL USE IN PHASE 2, LEADING TO FUTURE PHASE 1/2 CLINICAL TRIALS. THIS APPLICATION IS A SUBMISSION TO RFA-DA-25- 050, “SOLUTIONS TO ENABLE DIAGNOSIS AND TREATMENT OF ADVERSE HEALTH CONSEQUENCES OF NON-DISORDERED DRUG USE”. THIS PROPOSAL DIRECTLY ADDRESSES THE CRITICAL NEED OF DEVELOPING NEW THERAPEUTICS FOR TREATING NFOO-INDUCED BRAIN HYPOXIA.

NEURAL STEM CELL EXTRACELLULAR VESICLE TREATMENT FOR TRAUMATIC BRAIN INJURY - PROJECT SUMMARY/ABSTRACT TRAUMATIC BRAIN INJURY (TBI) IS A UNIVERSAL HEALTH CONCERN AND IS KNOWN AS A “SILENT EPIDEMIC”. EACH YEAR IN AMERICA, 2.53 MILLION PATIENTS VISIT THE EMERGENCY DEPARTMENT AFTER SUFFERING A TBI OF WHICH 56,800 DIE AND OVER 288,000 REQUIRE HOSPITALIZATION, REHABILITATION PROGRAMS, AND LONG-TERM SUPPORTIVE CARE. ALTHOUGH THE PRIMARY TBI EVENT IS TYPICALLY ACUTE, SUBSEQUENT SECONDARY INJURY RESPONSES (NEUROINFLAMMATION) AND CHRONIC TISSUE LOSS OFTEN RESULT IN FUNCTIONAL DEFICITS THAT LAST A LIFETIME. PRESENTLY, THERE ARE NO NEUROPROTECTIVE OR REGENERATIVE FOOD AND DRUG ADMINISTRATION APPROVED TBI TREATMENTS. ARUNA BIO HAS RECENTLY DEVELOPED A NOVEL NEUROPROTECTIVE AND REGENERATIVE NEURAL STEM CELL EXTRACELLULAR VESICLE (NSC EV) PRODUCT CALLED AB126™ THAT MAY BE USED TO TREAT TBI. AB126™ HAS DEMONSTRATED MULTIMODAL THERAPEUTIC EFFICACY IN DIVERGENT SPECIES (AGED MOUSE, RAT, PIG) AND NEURAL INJURY MODELS (TBI, STROKE). IN TBI RODENT MODELS, AB126™ REDUCED LESION SIZES, ENHANCED ENDOGENOUS NEUROGENESIS AND ANGIOGENESIS, AND RAPIDLY ATTENUATED MOTOR FUNCTION IMPAIRMENTS. LARGE ANIMAL TESTING HAS BEEN REPEATEDLY IDENTIFIED BY ACADEMIC, INDUSTRY, AND GOVERNMENT AGENCIES AS A KEY DE-RISKING STEP IN TBI THERAPEUTIC DEVELOPMENT. TO THIS END, THIS PROPOSAL OUTLINES FDA ENABLING STUDIES IN A PIG CONTROLLED CORTICAL IMPACT TBI MODEL USING CLINICALLY RELEVANT ASSESSMENT TOOLS TO EVALUATE THE EFFICACY AND SAFETY OF AB126™ AS A TREATMENT FOR TBI. THE SUCCESSFUL COMPLETION OF THIS STUDY WILL PROVIDE KEY INFORMATION PERTAINING TO AB126™ DOSAGE, THERAPEUTIC EFFECTS ON TBI PATHOPHYSIOLOGY (EDEMA, HEMORRHAGE) AND FUNCTIONAL OUTCOMES, TOXICITY, AND POTENTIAL ADVERSE SIDE EFFECTS THAT WILL SERVE AS THE BASIS FOR AN IND SUBMISSION AND FUTURE CLINICAL TRIALS.

AWARDTYPE: GUARANTEED/INSURED LOANS ACTIVITIES TO BE PERFORMED: TO PROVIDE GUARANTEED LOANS FROM LENDERS TO ELIGIBLE FOR PROFIT SMALL BUSINESSES WHICH ARE UNABLE TO OBTAIN FINANCING IN THE PRIVATE CREDIT MARKETPLACE BUT CAN DEMONSTRATE AN ABILITY TO REPAY LOANS IF GRANTED, IN A TIMELY MANNER. THE SBA GUARANTEES 7(A) PROGRAM LOANS THROUGH VARIOUS LOAN PROCESSING METHODS INCLUDING: (1) STANDARD 7(A) LOANS; (2) 7(A) SMALL LOANS; (3) SBAEXPRESS LOANS; (4) CAPLINE LOANS; (5) THE QUALIFIED EMPLOYEE TRUSTS (ESOP); (6) EXPORT EXPRESS; (7)EXPORT WORKING CAPITAL PROGRAM (EWCP); (8) INTERNATIONAL TRADE, AND (9) PILOT (TEMPORARY) PROGRAMS. DELIVERABLES: LOAN GUARANTEES EXPECTED OUTCOMES: TO PROVIDE GUARANTEED LOANS FROM LENDERS TO ELIGIBLE FOR PROFIT SMALL BUSINESSES AND, IN CERTAIN CIRCUMSTANCES, TO QUALIFIED EMPLOYEE TRUSTS (ESOPS). INTENDED BENEFICIARIES: SMALL BUSINESSES SUBRECIPIENT ACTIVITIES: NA