Successful Landmark Study in Paediatric ASD

A SX Announcement 5 April 2022 Neuro tech Internation al Ltd S uit e 5 CPC, 1 45 Stirl ing High w ay Ned l ands, W estern Aust ra li a 6009 T: +61 (8) 9389 3130 E: [email protected] W : neurotechinterna tion al.com ABN : 73 610 205 40 2 ASX: NTI 1 o f 7 Successful Landmark Study in Paediatric ASD Progresses to Pivotal Drug Registration Stage  Study demonstrate s safety and tolerability across the dosing regime  No Serious Adverse Events (SAEs) reported  Review of da ta to da te shows consi stent po sitive chan ges in tr ial patients for key be havioural indicators specifically relating to irritability, social interaction, mood and communication  Study scheduled t o progress to Phase II/III regist ration trial at Monash Children ’ s Hosp ital  D iscu ssions initiated with the TGA and NTI has initiated pre - IND activities in relation to US FDA Neurotec h International Limited (ASX: NTI) ("Neurotech" or "th e Company") is p leased to announce successful developments relating to safety and tolerability of NTI 164 and k ey behavio ural paramet ers th at impact A utism S pectrum D isorder ( ASD ) patients . NTI164 is one of NTI’s proprietary Dolce Cann Global cannabis strains in respect of neurological applications and is the world’s first full - spectrum medicinal cannabis prod uct (less than 0.3% THC) to be su ccessfully studied in children with ASD at Monash Children’s Hospital in Melbourne. The ongoing Study is designed to vigorously assess the safety and efficacy of NT I 164 in a dose escal ation reg ime and assess the behaviour, focus and cogn itive related para meters using validated neuro - psychological tools. Th is Study is designed to form the foundation fo r follow up studies in therapies relating to the treatment of a wide range of neuro logical disorders such as Multiple Sclerosis, M otor N eu ro n D isease, Rett’s Disease and Cerebral Palsy. Study Design and Outline:  Open label study .  The study populati on: children aged between eight years old through to seventeen year s that ha ve a medical diagnosis of Level II and III Autism Spectrum Di sorder ( ASD) as confi rmed b y the Autism Diagnostic Observational Schedule (ADOS - 2) criteria. Study Primary Endpoints:  S afety and tolerability - across dose regime (5mg/kg, 10mg/kg, 15mg /kg an d 20 mg/kg) .  Safety is monitored and meas ured by full blood exam inations , liver, and renal function tests in addition to parent/carer and physician questionnaires . Study Secondary En dpoints:  Efficacy monitored and measured through parent/carer and p hysician questionnaires to assess: – Irritability – Hyperactivity – Mood – Sel f - stimul ation – Sleep d isorde rs – Behavioural c rises – S ocial i nteraction – Comm u nication In total, over 2 , 250 assessment point s will be analysed through the landmark study . Study Outcomes to date :  D emonstrated safety and tolerability across t he dosing regime n .  No Serio us Adverse Ev ents ( SAEs) reported .  Patients are showing positive trends and improvements compared to their baseline assessments measured a t the commencement of the trial.  Improvements were observed with trial patients in key beh avioural indicator s relate d to irritabi lity, social interaction, mood and communication.  The improvements were unique to each trial participant given the complexiti es of how ASD affects children. The rigorous clinical study design involves assessments and feedback from the neur opsychologist monit oring tria l participants, the parents/carers, and the participants themselves. Most importantly, parental/carer observat ions cite consistent improvement in the trial participant’s ‘overall functioning’ when comp ared to baseline a t the co mmencement of the t rial. Specific instances of markedly improved behaviours ( i.e . reduction in fear, agitation and anxiety) are being further investigated to fully assess and understand the positive neuro - psychological impact of NTI164 treatment in these patients. T his re sear ch along with further data assessment from the Trial will be completed in Q2. These key areas of neuro - behavioural change will be the key focus of the upcoming drug registration trials due to commence in Q3 ca lendar 2022 . Th e only dru g currently appr o ved by the FDA for children with ASD is Risperidone. P rescribed for children to assist with irritability , c om mon side effects include headaches, drowsiness, anxiety and uncontrollable muscle movements. Gi ven the NTI trial results showed no serious a d verse side effects and high patient compliance, we believe the Company is very well placed to make significant inro ads into the AS D treatm e n t market expected to be around US$5.5bn by 2028 * . “We are very pleas ed wi th the landmark resul ts from ou r world fir st tri al. NTI has the pot ential to introduce to the market a treatment option for paediatric ASD which is natural, safe and based on the results to date, offers positive behavioural improvements in ASD , ” sa id Company Chairman Brian Lee dman . “ We will move q uickly to a Phas e II/III drug registration trial , initiate TGA and FDA pathways and expedite strategic partner discussions . ” Newly appointed CEO, Dr Alexandra And rews said, “ The Company has acceler ated it s commercial discussions with several s trategic ph armace utical companies who have been following the trial ’ s progress . What cannot be un der estimated i s the application of our full spectrum strain to other neurological disorders which will now be accel erate d considering the current ASD results . ” * https:// www.gl obenewswire.com/news - release/2021/12/14/2351376/ 0/en/Autism - Spectrum - Disorder - Therapeutics - Marke t - Size - 2021 - 2028 - is - Expected - to - be - Worth - USD - 5 - 15 - Billion.html) The Company has initiated discussions wi th the Therapeutics Good Admi nistration (TGA) to a ssess product scheduling and classification for the Aus tralian Market. In collaboration with regulator y experts, the Company is now mapping out a full regulatory development roadmap/pathway for the registra tion and commercialisation of NTI164 fo r ASD and o ther n eurological indications. The Company has initiat ed pre - IND (Investigational New Drug) discussion s with the FDA and is the process of developing a clear roadmap for product registration and commercial development in the USA. Auth ori ty T his anno u nceme nt has been author ised for rel ease by t he Boar d of Neurotech International Limi ted. Further Inform a tion Dr Alexandra Andrews CEO [email protected] +61 (0)405 339 788 Brian Leed man Chairma n b.leedm an@neurotechint ern at ional.com +61 (0)41 228 17 8 0 M edia: Am a li e Schreu rs White Noise Comm uni cat ions amali e @whitenoise comms.com +61 (0) 431 63 6 033 About Ne urotech Neurote ch Inte rnational Limi ted is a medical d evice and solutions com pany cond ucting clinic al studies to ass ess the ne uro - prote ct iv e, a nti - inflammatory and neu ro - modulator y activities of our proprietary NTI/Dolce cannabi s strai ns. Neurotech has submitted key provisional patent s relating to the composition and use of NTI164 for the t reatment of a range of neurolo gic al diso rders inclu ding A S D. Neurotech is al so commercialisi ng Ment e, the world’s first home therap y that is clinically pr oven to increase engag ement and i mprove relaxatio n in auti stic c hildr en with elevated Delt a b and brain activity. For more informatio n about Ne urotech a nd Ment e Aut ism please visi t http://www.neu rotechi nternational.c om APPENDIX - Study Details This stu dy is conducted in accordance with this protocol, ICH GCP guidelines, federal and local governing regula tory requirements and laws and in accord ance with H REC gu idelines. Title: Phase I/II Open – Label Study to Evaluate the Safety and Efficacy of Orally A dministered Full - Spectrum Medicinal Cannabis Plant Extract (0.08% THC) – NTI164 in Children with Autism Spectrum Disorder . Site: Mona sh Childre n’s Hospita l Clay ton, Melbourne Victoria . Study Population : Aged between 8 to 17 years old population that have a medical diagnosis of Level 2 or 3 Autism Spectrum Disorder (ASD) as confirmed by the Autism Diagnosti c Observati onal Schedule (ADOS - 2) criter ia. Subjec t incl usion criteria:  Participant is aged 8 years to 17 years (inclusive) .  Participant is at a he althy weight at the discretion of the Principal Investigator.  Parents or caregivers can give informed consent for participation in the tri al with as sent from i ndivid uals with autism.  Participants can comply with trial requirements.  According to the Diag nostic and Statistical Manual of Mental Disorders, 5th Edition (DSM - 5) criteria the participant has a di agnosis of Level 2 or 3 autism spectr um disorde r (ASD) confir med by Autism Diagnostic Observational Schedule (ADOS - 2) criteria .  All treatments includi ng medications and therapies for ASD related symptoms must have been stable for 4 weeks before enrolment and for the duration of the trial wher ever possi ble.  Participa nts mu st be able to swallow liquid.  Consent giver must be able to understand the requ irements of the study. Subject exclusion criteria :  Current diagnosis of bipolar disorder, psychosis, schizophrenia, schizoaffective disorder, or a ctive majo r depression .  Has a diagnosis other than ASD that dominates the clinical presentation (e.g., at tention deficit hyperactivity disorder [ADHD]) .  Has a degenerative condition .  Changes in ant iconvuls ive therapy within the last 12 weeks .  Taking omepra zole, lans oprazole, tolb utamid e, warfarin, sirolimus, everolimus, temsirolimus, tacrolimus, clobaza m, repaglinide, pioglitazone, rosiglitazone, montelukast, bupropion, or efavirenz .  Currently using or has used recreational or medicinal cannabis, cannabinoi d - based me dications (inc luding Sativex or Epidiolex ) within the 12 weeks prior to screening and i s unwilling to abstain for the duration of the trial .  Participant has any known o r suspected hypersens itivity to cannabinoids or any of the excipients .  Partici pant has m oderately impa ired h epatic function at screening, defined as serum alanine aminotra nsferase (ALT) or aspartate aminotransferase (AST) > 2 Å~ upper limit of normal (ULN ) or total bilirubin (TBL) > 2 Å~ ULN. This criterion can only be confirmed onc e the labo ratory results are a vailable; participants enrolled into the trial who are later fo und to meet this criterion must be screen - failed.  Participant is male and fertile (i.e., after puberty unless permanently sterile by bilateral orchidectomy) unless willing t o ensure that they u se male contraception (condom) or remain sexually abstinent d uring the trial and for 12 weeks thereafter.  Participant is female and with childb earing potential (i. e., following menarche and until becoming postmenopausal for ≥ 12 consecutive months un less p ermanently sterile by hysterectomy, bilateral salpingectomy , or bilateral oophorectomy) unless willing to ensure that they use a highly effecti ve method of birth c ontrol (e.g., hormonal cont raception, intrauterine device/hormone - releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence) during the trial and for 12 weeks thereafter.  Female participant who is pregnant ( positive pregnancy t est), lactating or planning p regnancy during the course of the trial or within 12 weeks thereafter.  Participant had brain surgery or traumatic brain i njury within 1 year of screening.  Participant has any other significant disease or disorder which, in the opinion of the investigator, may either put the participant, other participants, or site staff at risk because of participation in the trial, may in fluence the result of the trial, or may affect the participant's ability to take par t in the trial.  An y abnormalities identified followin g a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if they took part in the trial .  Any history of suicidal behaviour (lifelong) or any su icidal ideation of type 4 or 5 on the Columbia - Suicide Severity Rating Scale (C - SSRS) in the last 4 weeks or at screening or randomization .  Participan t has donated blood during the past 12 weeks and is unwilling to abstain fr om donation of blood during t he trial.  Participant has any known or suspected history of alcohol or substance abuse or positive drugs of abuse test at screening (not justified by a known concurrent medication).  Participant has previously been enrolled into this trial.  Participan t has plans to travel outside their country o f residence during the trial, unless the participant has confirmation that the product is permitted in the destination country/state . Assessments of efficacy: Efficacy will be monit ored and measured through par ent/carer and physician questionnaires . The secondary outcomes measures listed below will be used to assess potential improvements of:  Irritability  Hyperactivity  Mood  Self - stimulation  Sleep disorders  Seizures  Behavioural Crises  Social Int eraction  Communication Secondary Endpoints 1. Social Respons iveness Scale, 2nd Edition (SRS - 2), School - Age Form Five domains are assessed including: Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests an d Repetitive Behaviour. Items are scored on a 4 - point scale (ra nging from 1=not true to 4=almost always true). 2. Anxiety, Depression and Mood Scale (A DAMS) 28 symptom items that resolve into fi ve subscales labelled: Manic/Hyperactive Behaviour, Depresse d Mood, Social Avoidance, General Anxiety, and Compulsive Behav iour. Items are rated on 4 - point scale ranging from 0=not a problem to 3=severe problem. 3. Sleep Disturbance Scale for Children (SD SC) Six subscales including Disorders of Initiating and Main taining Sleep, Sleep Breathing Disorders, Disorders of Arousal, Sleep Wake Transition Disorders, Disorders of Excessive Somnolence, and Sleep Hyperhydro sis. Items are rated on 5 - point scale where 1=never and 5=always (daily). Subscale scores sum to equal a total score . 4. Clinical Global Impression - Severity (CGI - S) R eflects clinician’s impression of severity of illness on a 7 - point scale ranging from 1=n ot at all to 7=among the most extremely ill. 5. Autism Family Experience Questionnaire (AFEQ) Parent/Ca regiver form used to measure impact of autism interventions on family experience and quality of life. Items are rated on a 5 - point scale where 1=always and 5=never. 6. Anxiety Scale for Children - Autism Spectrum Disorder - Parent Versions (ASCASD - P) Pare nt/Caregiver form developed to detect symptoms of anxiety in yo uth with ASD. Composed of four subscales (Performance Anxiety, Uncertainty, Anxious Arous al, and Separa tion Anxiety), items are rated on a 4 - point scale (0=never and 3=always). Subscales sum to equal a total score. 7. Anxiety Scale for Children - Autism S pectrum Disorder (ASC - ASD - C) - Child Versions Child form developed to detect symptoms of anxiety in you th with ASD. Composed of four subscales (Performance Anxiety, Uncertainty, Anxious Arousal , and Separation Anxiety), items are rated on a 4 - point scale ( 0=never and 3=always). Subscales sum to equal a total score. 8. The Child Behaviour Chec klist for Ages 8 – 1 7 (CBCL) A parent/carer measure to assess patterns of behaviour. The measure is a Likert scale rated over 3 or 4 points. 9. Caregiver Global Impre ssion of Change in Attention (CGI - CA) Reflects clinician’s impression of change in atte ntion on a 7 - po int scale ranging from 1=not at all to 7=very severe problem. Provided as Baseline and Po st - Baseline questionnaires. 10. Caregiver Global Impression of Change (CGI - C) Target Behaviour Reflects clinician’s impression of change of behaviour on a 7 - point scale ranging from 1=not at all to 7=very severe problem. Provided as Baseline and Post - Bas eline questionnaires. 11. Clinical Global Impression Scale - Imp rovement (CGI - I) This is a 7 - point scale measuring symptom change from baseline. Provid ed as baseline and post - baseline Caregiver and Clinician questionnaires. 1 2. Vineland Adaptive Behaviou r Scales, Third Edition (Vineland - 3) Parent/Caregiver Form. Used to measure adaptive functioning across three core domains (Communication, Daily L iving Skills, and Socialization), and two optional domains (Motor Skills and Maladaptive Behaviour); items are rated on a 3 - point scale (0=never; 1=sometimes; 2=usually or oft en). The core domains sum to a total Adaptive Behaviour Composite.

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