Kino Inc

ADVANCING KNX100 FOR THE TREATMENT OF OPIOID WITHDRAWAL: PRECLINICAL EFFICACY AND TOXICOLOGY, AND A PHASE 1 CLINICAL PROGRAM. - APPLICATION IDENTIFIER: 364510 APPLICATION PROJECT TITLE: ADVANCING KNX100 FOR THE TREATMENT OF OPIOID WITHDRAWAL: PRECLINICAL EFFICACY AND TOXICOLOGY, AND A PHASE 1 CLINICAL PROGRAM. PROJECT SUMMARY/ABSTRACT KINOXIS THERAPEUTICS PTY LTD IS AN AUSTRALIAN BASED COMPANY THAT HAS LICENSED INTELLECTUAL PROPERTY FROM THE UNIVERSITY OF SYDNEY, INCLUDING SEVERAL CANDIDATES FOR THE TREATMENT OF SUBSTANCE USE DISORDERS. WE HAVE DEVELOPED A NOVEL SMALL MOLECULE LEAD, KNX100, WHICH IS SHOWING CONSIDERABLE PROMISE IN PRECLINICAL ANIMAL MODELS OF A RANGE OF SUBSTANCE USE DISORDERS, INCLUDING MODELS OF OUD, WITH PARTICULARLY IMPRESSIVE EFFICACY AT REDUCING THE SEVERITY OF OPIOID WITHDRAWAL SYMPTOMS IN MICE. KNX100 WAS DISCOVERED FROM A PHENOTYPIC SCREEN OF COMPOUNDS DERIVED FROM A FRAGMENT-BASED DRUG DISCOVERY PROGRAM TARGETING THE BRAIN OXYTOCIN SYSTEM. KNX100 HAS A FAVORABLE PHARMACOKINETIC AND SAFETY PROFILE IN TESTING THUS FAR. TO DATE, KNX100 HAS UNDERGONE TESTING FOR EFFICACY SIGNALS IN TWO RODENT AND TWO NON-HUMAN PRIMATE SPECIES, WITH TESTING TAKING PLACE ACROSS MULTIPLE LABORATORIES INCLUDING NATIONAL INSTITUTE ON DRUG ABUSE (NIDA) COMMISSIONED LABORATORIES UNDER THE NIDA MEDICATIONS DEVELOPMENT PROGRAM. THE PROPOSED ACTIVITY UNDER THIS FUNDING OPPORTUNITY IS TO PROGRESS THE DEVELOPMENT OF KNX100 IN OPIOID USE DISORDER, WITH THE SPECIFIC INDICATION BEING TREATMENT OF OPIOID WITHDRAWAL. THE OVERALL OBJECTIVE OF THE PROJECT IS TO ESTABLISH THE SAFETY AND TOLERABILITY OF KNX100 TO ENABLE HUMAN EFFICACY TESTING TO COMMENCE IN PATIENTS REQUIRING TREATMENT FOR OPIOID WITHDRAWAL. THE LONG-TERM OBJECTIVE FOR THIS DEVELOPMENT PROGRAM IS TO GENERATE HUMAN EFFICACY DATA TO SUPPORT KNX100 AS A POTENTIAL TREATMENT FOR OPIOID WITHDRAWAL SYMPTOMS AND ULTIMATELY ENABLE A NEW DRUG APPLICATION TO THE FDA. THE COMPANY HAS DEVELOPED A RESEARCH PLAN WHICH ENTAILS BOTH A UG3 PHASE AND A UH3 PHASE. FOR THE UG3 PHASE, THE COMPANY PLANS TO COMPLETE ALL THE NECESSARY IND ENABLING STUDIES REQUIRED FOR FDA APPROVAL TO ADMINISTER KNX100 IN A FIRST IN MAN, PHASE 1 CLINICAL STUDY. THE PROGRAM INCLUDES ADDITIONAL TESTING OF KNX100 IN ANIMAL MODELS OF OPIOID WITHDRAWAL; SCALE UP AND MANUFACTURE OF DRUG SUBSTANCE AND DRUG PRODUCT TO SUPPORT BOTH THE NON-CLINICAL AND CLINICAL PROGRAMS; A TOXICOLOGY PROGRAM TO GENERATE DATA TO SUPPORT THE PHASE 1 STUDY; AND THE SUBMISSION OF AN INVESTIGATIONAL NEW DRUG APPLICATION TO THE FDA. FOLLOWING THE SUCCESSFUL COMPLETION OF THE UG3 PHASE, MEASURED BY THE MILESTONE OF FDA CLEARANCE OF AN IND APPLICATION TO A COMMENCE A PHASE 1 STUDY WITHOUT A CLINICAL HOLD, THE COMPANY WOULD THEN PROGRESS INTO THE UH3 PHASE BY COMPLETING A PHASE 1 CLINICAL PROGRAM TO ESTABLISH THE SAFETY AND TOLERABILITY OF KNX100 WHEN DOSED IN HUMANS. THE PURPOSE OF THIS NIH/NIDA FUNDING OPPORTUNITY ANNOUNCEMENT (RFA-DA-19-002), FOR WHICH THIS APPLICATION IS BEING SUBMITTED, IS TO SUPPORT THE DISCOVERY AND DEVELOPMENT OF MEDICATIONS TO PREVENT AND TREAT OPIOID USE DISORDERS (OUD) AND OVERDOSE. THE DEVELOPMENT OF KNX100 OFFERS AN OPPORTUNITY TO PROVIDE A MORE EFFICACIOUS AND/OR SAFER ALTERNATIVE TO THE CURRENT ONLY APPROVED MEDICATION FOR OPIOID WITHDRAWAL, LOFEXIDINE, AND THIS APPLICATION WILL ACCELERATE THE DEVELOPMENT TOWARD THIS OBJECTIVE.

ADVANCING KNX100 FOR THE TREATMENT OF OPIOID WITHDRAWAL: PRECLINICAL EFFICACY AND TOXICOLOGY, AND A PHASE 1 CLINICAL PROGRAM.

INTEGRATED ENVIRONMENTAL AND DISEASE SURVEILLANCE IN VIETNAM

MICROFLUIDIC SYSTEM FOR COMPLETE AND AUTOMATED DISSOCIATION OF TUMOR TISSUE INTO SINGLE CELLS - ABSTRACT SOLID TUMORS CONTAIN DIVERSE CELLULAR ECOSYSTEMS, AND THIS HETEROGENEITY HAS BEEN IMPLICATED AS A KEY FACTOR DRIVING DISEASE PROGRESSION, METASTASIS, AND DRUG RESISTANCE. HENCE, IDENTIFYING THE PRESENCE AND FUNCTION OF EACH CELL SUBTYPE IS NEEDED TO FULLY UNDERSTAND TUMOR DRIVERS AND GUIDE THERAPEUTIC DECISIONS. INCREASINGLY, SINGLE CELL ANALYSIS METHODS ARE BEING USED TO DEFINE CELLULAR SUBSETS WITHIN TUMORS TO ADDRESS BIOLOGICAL AND THERAPEUTIC QUESTIONS. A METHOD THAT IS RAPIDLY EMERGING IS SINGLE CELL RNA SEQUENCING (SCRNA-SEQ), WHICH ENABLES IDENTIFICATION OF CELL TYPE AND FUNCTION BASED ON THE TRANSCRIPTOME. HOWEVER, TUMOR TISSUE MUST FIRST BE CONVERTED INTO SINGLE CELLS, AND THIS STEP IS A CRITICAL BARRIER TO MORE WIDESPREAD USE OF SINGLE CELL ANALYSIS METHODS, PARTICULARLY IN CLINICAL SETTINGS. STANDARD TISSUE DISSOCIATION PROTOCOLS INVOLVE SEVERAL MANUAL STEPS THAT ARE SLOW, INEFFICIENT, AND HIGHLY VARIABLE. COMMERCIAL SYSTEMS ONLY ACCOMPLISH PART OF THE WORKFLOW AND ARE NOT WELL-CHARACTERIZED. IN PREVIOUS WORK, WE DEVELOPED NOVEL MICROFLUIDIC DIGESTION, DISSOCIATION, AND FILTRATION DEVICES THAT UTILIZED HYDRODYNAMIC FORCES TO BREAK DOWN TISSUE INTO SINGLE CELLS. WE RECENTLY COMBINED THE DEVICES INTO A PLATFORM AND ATTAINED EXCELLENT RESULTS FOR VARIOUS MURINE TISSUES, INCLUDING BREAST TUMORS. SPECIFICALLY, THE DEVICE PLATFORM SIGNIFICANTLY ENHANCED SINGLE CELL RECOVERY AND DECREASED CELL SUBTYPE BIASING. TO DATE, THESE DEVICES HAVE NOT BEEN APPLIED TO HUMAN TUMOR SPECIMEN. IN THIS PROPOSAL, WE WILL DEVELOP A POWERFUL TUMOR DISSOCIATION PLATFORM THAT CAN PERFORM THE ENTIRE WORKFLOW IN A FAST, EFFICIENT, AND GENTLE MANNER. WE WILL FOCUS ON CREATING A PROTOTYPE BENCHTOP FLUIDIC SYSTEM THAT CONTAINS ALL OF THE NECESSARY COMPONENTS (I.E. PUMPS, VALVES, MONITORING CAPABILITIES, CONTROL SOFTWARE) TO OPERATE THE MICROFLUIDIC CARTRIDGES IN AN OPTIMAL AND AUTOMATED MANNER. WE WILL FIRST CREATE THE SYSTEM AND PERFORM BASIC FEASIBILITY AND QUALITY CONTROL TESTS. WE WILL THEN OPTIMIZE PERFORMANCE OF THE FLUIDIC SYSTEM AND MICROFLUIDIC CARTRIDGES USING A MURINE BREAST TUMOR MODEL, WITH SINGLE CELLS ANALYZED BY FLOW CYTOMETRY AND SCRNA-SEQ. AS PART OF THIS WORK, WE WILL ALSO INCREASE TISSUE SAMPLE SIZE SO THAT ENTIRE TUMOR RESECTIONS CAN BE PROCESSED. FINALLY, WE WILL PERFORM A SMALL VALIDATION STUDY USING HUMAN BREAST TUMOR SPECIMENS. THE SPECIFIC AIMS FOR THIS 6 MONTH PROJECT INCLUDE (1) CREATE THE PROTOTYPE FLUIDIC SYSTEM, (2) OPTIMIZE FLUIDIC SYSTEM USING MURINE TUMOR TISSUE, AND (3) VALIDATE PERFORMANCE USING HUMAN BREAST TUMOR SPECIMEN. THE SINGLE CELL ANALYSIS MARKET IS EXPECTED TO GROW ROBUSTLY, DRIVEN BY GROWING BIOTECHNOLOGY AND PHARMACEUTICAL INDUSTRIES, RISE IN SINGLE CELL GENOMICS, AND APPLICABILITY TO CANCER FOR BASIC RESEARCH AND PERSONALIZED MEDICINE. OUR MICROFLUIDIC DISSOCIATION TECHNOLOGIES ARE POISED TO MAKE A SIGNIFICANT IMPACT ON THE SINGLE CELL ANALYSIS OF TUMOR TISSUES BY MAKING IT EASIER AND MORE RELIABLE TO PREPARE SAMPLES. THERE IS MINIMAL COMPETITION AT THIS TIME, AND WE ARE POSITIONED TO OFFER THE ONLY SOLUTION THAT CAN PERFORM ALL TASKS IN THE TISSUE PROCESSING WORKFLOW AND, MOST IMPORTANTLY, ACHIEVE PERFORMANCE METRICS THAT CANNOT BE MATCHED. A PORTFOLIO CONTAINING 7 PATENTS THAT HAVE ISSUED OR ARE PENDING IS CURRENTLY BEING LICENSED BY KINO DISCOVERY. THE RESEARCH PLAN WAS DIRECTLY INFORMED BY EXTENSIVE MARKETING DISCUSSIONS WITH LEADING PHARMACEUTICAL, BIOTECHNOLOGY, AND LIFE SCIENCE COMPANIES THROUGH A MICROFLUIDIC-BASED CENTER AT UC IRVINE AND THE MEDTECH INNOVATOR BIOTOOLS PROGRAM.

TO ENHANCE THE PROFESSIONALIZATION OF JOURNALISM AND STRENGTHEN DEMOCRATIC CAPACITIES BY RAISING THE LEVEL OF MEDIA LITERACY AND DEVELOPING CRITICAL INTERPRETATION OF MEDIA CONTENT.

PURPOSE OF THIS PROJECT IS TO CONTRIBUTE TO THE ELIMINATION OF MENSTRUATION (AND MENOPAUSE) STIGMA IN LITHUANIA BY USING CINEMA AS A TOOL FOR EDUCATION.

TO CONTRIBUTE TO ACTIVE SOCIAL INCLUSION OF YOUNG PEOPLE WITH DISABILITIES BY SUGGESTING A NON-FORMAL EDUCATION COURSE ON SOCIAL MEDIA ACTIVITIES.

SUPPORT MOVIE SCREENINGS AND SPECIAL EVENTS WITH U.S. ARTIST THAT ARE RAISING AWARENESS ABOUT RACE, DIVERSITY AND MINORITY GROUPS.

SUPPORT THE MFF FILMMAKING WORKSHOP THAT FOSTERS A CROSS-CULTURAL DIALOGUE VIA DIGITAL STORYTELLING AMONG YOUTH AND CREATIVE COMMUNITY, LED BY EXPERIENCED AMERICAN EDUCATORS, RESULTING IN TWO STUDENT FILMS BEING SCREENED AT CLOSING NIGHT OF THE FESTIVAL.

TO SUPPORT THE 20TH MEDITERRANEAN FILM FESTIVAL

TO SCREEN A SELECTION OF AMERICAN FILMS AT THE 19TH MILLENNIUM DOCS AGAINST GRAVITY FESTIVAL IN POLAND.

TO SCREEN A SELECTION OF AMERICAN FILMS AT THE 18TH MILLENNIUM DOCS AGAINST GRAVITY FILM FESTIVAL IN POLAND.

IMPLEMENTATION OF A PROGRAM THAT WILL OFFER A BROAD LOOK AT CONTEMPORARY AMERICAN LIFE AND THE VALUES OF A FREE AND DEMOCRATIC SOCIETY.

ADVANCES CROSS-CULTURAL DIALOGUE VIA DIGITAL STORYTELLING AMONG YOUTH, EDUCATORS AND CREATIVE COMMUNITY WITH PARTICIPATION OF EXPERIENCED AMERICAN EDUCATORS, RESULTING IN TWO STUDENT FILMS BEING SCREENED AT THE 22ND MFF

SUPPORT OF PARTICIPATION OF U.S. ARTISTS AND MUSIC PROFESSIONALS AT MENT LJUBLJANA 2018 FESTIVAL.

TO FUND THE 18TH MEDITERRANEAN FILM FESTIVAL OF DOCUMENTARY FILMS AND MFF SCHOOL CONDUCTED BY U.S. AND BIH PROFESSIONALS FOR U.S. AND BIH STUDENTS

RETROSPECTIVE FILM PROGRAM THE ROSSELLINIS AND THE CENTURY WITH THE PARTICIPATION OF ISABELLA ROSSELLINI AND ALESSANDRO ROSSELINI AT THE RIGA IFF 2021.

THIS AWARD IS TO PRESENT AN AMERICAN FILM CLASSIC THE MAGNIFICENT SEVEN AT THE OPEN-AIR CINEMA AT CONGRESS SQUARE IN THE CENTER OF LJUBLJANA.

TO FUND THE MEDITERRANEAN FILM FESTIVAL OF DOCUMENTARY FILMS AND MFF SCHOOL CONDUCTED BY US AND BIH PROFESSIONALS FOR US AND BIH

THIS AWARD SUPPORTS THE PRESENTATION OF A FILM CLASSIC NOTORIOUS, DIRECTED AND PRODUCED BY ALFRED HITCHCOCK AT THE ONE OF THE MOST POPULAR SUMMER FILM FESTIVALS IN SLOVENIA.

THIS AWARD SUPPORTS THE PRESENTATION OF THE FOLLOWING FIVE FILMS NOIR: THE KILLERS, DOUBLE INDEMNITY, MILDRED PIERCE, CRISS CROSS AND DETOUR. THE AIM OF THIS PROJECT IS TO BRING FILM CLASSICS CLOSER TO THE SLOVENIAN AUDIENCES.

TO SUPPORT A VISIT OF A MEMBER OF THE AMERICAN CINEMA FOUNDATION WHO WILL BE A PART OF AN INTERNATIONAL JURY AT VILNIUS INTERNATIONAL FILM FESTIVAL,

THIS AWARD IS TO SUPPORT AN AMERICAN MUSIC DOCUMENTARY PRESENTED IN THE FRAME OF KINODVOR'S FESTIVAL IN JUNE OF 2019.

THIS AWARD IS TO PRESENT AN AMERICAN FILM CLASSIC NINOTCHKA AT THE OPEN-AIR CINEMA AT CONGRESS SQUARE IN THE CENTER OF LJUBLJANA.

U.S. SPEAKER ATTENDS RIGA IFF, GIVING HIS EXPERTISE THROUGH LECTURE, INDIVIDUAL CONSULTATIONS AND AS JUDGE IN HACKATHON.

PROMOTING THE U.S. CULTURE THROUGH A SCREENING OF SIX FILMS FEATURING VIGGO MORTENSEN, ACCOMPANIED BY AN EXHIBITION IN HONOR OF THIS GREAT ARTIST.

PRESENTATION OF AN AMERICAN FILM, ENTITLED HUMMINGBIRDS, AT THE 8TH KINOTRIP INTERNATIONAL FILM FESTIVAL, FESTIVAL BY THE YOUTH FOR THE YOUTH, TO DRIVE DISCUSSION AND BUILD SUPPORT FOR DEIA PRINCIPLES

THIS 12-HOUR FILM MARATHON WILL FEATURE TWO OF THE AMERICAN HORROR FILM CLASSICS. IT IS ONE THE MOST SUCCESSFUL PROGRAM OF KINODVOR.

THE AWARD WILL COVER TRAVEL AND ACCOMMODATION COSTS RELATED TO U.S. FILM THEORIST DUDLEY ANDREW PROFESSOR FROM YALE UNIVERSITY HOLDING A LECTURE AT

SUPPORT FOR INDEPENDENT FILM FESTIVAL - "AMERICAN INDEPENDENT" FILM SERIES

TO COVER PARTIAL COST CONNECTED WITH ORGANIZING "SILENT FILM FESTIVAL" IN KRAKOW DECEMBER 10-13 2009.

THIS AWARD SUPPORT PRE-SCREENING OF THE DOCUMENTARY ON U.S. EFFORTS TO TACKLE CLIMATE CHANGE AND BUILD A MORE RESILIENT ENERGY FUTURE. IT IS AN OUTCOME OF THE FOREIGN PRESS CENTERS MEDIA CO-OP PROGRAM IN THE UNITED STATES.

SUPPORT PARTICIPATION OF THE US FILM COMPOSER BRIAN MCOMBRE IN RIGA INTERNATIONAL FILM FESTIVAL, SEPTEMBER 2017, RIGA, LATVIA.

THIS AWARD WILL SUPPORT THE SCREENING OF THE HISTORICAL DOCUMENTARY ENTITLED MISSION TO MT. MANGART - AN UNTOLD 10TH MOUNTAIN DIVISION STORY OF WORLD WAR II IN LJUBLJANA, ON JUNE 6.