Full Press Release Details
Corporate Presentation Nasdaq: BNOX ASX: BNO H.C. Wainwright BIOCONNECT Virtual Conference January 10 - 13, 2022
SAFE HARBOR STATEMENT 2 Factors Affecting Future Performance This
presentation may contain forward-looking statements within the meaning of the United States' Private Securities Litigation Reform Act of 1995. Any statements contained in this presentation that relate to prospective events or developments,
including, without limitation, statements made regarding Bionomics' drug candidates (including BNC210, BNC105, BNC101 and BNC375), its licensing agreement with Merck & Co. and any milestone or royalty payments thereunder, drug discovery
programs, ongoing and future clinical trials, and timing of the receipt of clinical data for our drug candidates are deemed to be forward-looking statements. Words such as believes, anticipates, plans, expects, projects, forecasts, will and similar
expressions are intended to identify forward-looking statements. There are a number of important factors that could cause actual results or events to differ materially from those indicated by these forward-looking statements, including unexpected
safety or efficacy data, unexpected side effects observed in clinical trials, risks related to our available funds or existing arrangements, delays or difficulties associated with conducting clinical trials, our failure to introduce new drug
candidates or platform technologies or obtain regulatory approvals in a timely manner or at all, regulatory changes, inability to protect our intellectual property, risks related to our international operations, as well as other factors. Results of
studies performed on our drug candidates and competitors' drugs and drug candidates may vary from those reported when tested in different settings. The inclusion of forward-looking statements should not be regarded as a representation by
Bionomics that any of its expectations, projections or plans will be achieved. Actual results may differ from those expectations, projections or plans due to the risks and uncertainties inherent in Bionomics business and other risks described in
Bionomics' filings with the SEC. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor, or
combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although we believe
that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any
forward-looking statements for any reason after the date of this presentation. Subject to the requirements of any applicable legislation or the listing rules of any stock exchange on which our securities are quoted, we disclaim any intention or
obligation to update any forward-looking statements as a result of developments occurring after the date of this presentation. Certain information contained in this presentation relates to, or is based on, studies, publications, surveys and other
data obtained from third party sources and Bionomics' own internal estimates and research. While we believe these third party sources to be reliable as of the date of this presentation, we have not independently verified, and make no
representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and
there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.
Emerging Leader in Neuropsychiatry 3 Diversified, clinical-stage
biopharmaceutical company developing novel, allosteric ion channel modulators designed to transform the lives of patients suffering from serious Central Nervous System (CNS) disorders 1 BNC210 in ongoing Phase 2 for acute treatment in Social Anxiety
Disorder (SAD) - Established clinical PoC in GAD and Fast Track designation from FDA for SAD BNC210 in ongoing Phase 2b ATTUNE trial with Fast Track designation from FDA for PTSD Large underserved markets with over 22 million patients in the
United States alone suffering from SAD and PTSD and no new FDA approved therapies in nearly two decades Strategic partnership with Merck & Co. for cognitive impairment in Alzheimer's disease and other CNS conditions Pipeline of partnering
candidates targeting potassium (Kv) and sodium (Nav) ion channels Well-capitalized balance sheet with multiple potential near term value-driving milestones PoC = Proof of Concept GAD = Generalized Anxiety Disorder PTSD = Post-Traumatic Stress
Disorder 1. Wise et al 2020, Biological Psychiatry; Perkins et al 2021, Molecular Psychiatry
Focused CNS Pipeline with Multiple Potential Catalysts on the Horizon 4
` PROGRAM PRECLINICAL PHASE 1 PHASE 2 PHASE 3 EXPECTED TIMING Post-Traumatic Stress Disorder (PTSD) Study underway 200 patients across ~25 centers in US Study Topline Data: 1H'23 Social Anxiety Disorder (SAD) BNC210 Study underway 150 patients
across ~15 centers in US Study Topline Data: YE'22 7 receptor NAM +MDMA derivative Memorandum of Understanding to explore Ongoing EMP-01 (PTSD) combination treatment regimen for PTSD Phase 1 safety & 2 candidates for cognitive
deficits biomarker studies in Alzheimer's disease COLLABORATION ongoing 7 receptor PAM PAIN Candidate Nav1.7/1.8 Inhibitors Ongoing COGNITION Series Lead Kv3.1/3.2 Activators NAM = Negative Allosteric Modulator PAM = Positive Allosteric
A Differentiated Approach: The a7 Nicotinic Acetylcholine Receptor 5
Normalizing Effect Utilizing Allosteric Modulation Targeting Distinct CNS Conditions with Neurotransmitter Imbalance 1 2 2+ Ca flow Channel opens: through the 2+ Ca ACh binds to channel when BNC 210 (NAMs) a7 receptor a7 receptors + Anxiety
orthosteric + PTSD are activated sites + Depression Hypercholinergic Disease States Transmembrane Binding Domain Hypocholinergic Disease States 3 4 PAM PAMs / NAMs Allosteric drug Indications bind to a7 transmembrane binding 2+ receptor Ca domain
restores normal allosteric sites activity 2+ Ca = Calcium ions ACh = Acetylcholine NAM = Negative Allosteric Modulator PAM = Positive Allosteric Modulator Cholinergic = System associated with memory, selective attention, and emotional processing
cognitive functions PTSD = Post-Traumatic Stress Disorder CIAS = Cognitive Impairment Associated with Schizophrenia ADHD = Attention Deficit Hyperactivity Disorder
Harnessing the Power of a Novel Neuromodulatory Mechanism 6 ANXIETY
& NORMAL Action of BNC210 PTSD depends on Acetylcholine neurotransmission NORMAL BNC210 RESTORES and Allosteric ACh MOOD NORMAL MOOD 2+ Ca Modulation of BNC210 MOOD DISORDERS a7 nAChR NAMs have self-limiting activity determined by the
cooperative interaction between BNC210 and Acetylcholine binding at the allosteric and orthosteric sites, respectively nAChR = Nicotinic Acetylcholine Receptor NAM = Negative Allosteric Modulator 2+ Ca = Calcium ions ACh = Acetylcholine
7 BNC210 in Social Anxiety Disorder
Targeting a Large Segment of the Anxiety Market 8 Acute Anxiety in SAD
Represents a Significant Unmet Need Social Anxiety Disorder (SAD), or Social Phobia, is a significant and persistent fear of social and ~31M performance-related situations 12.1% of adults at some point Includes anxiety from everyday social
situations as in their lives well as "Fear of Public Speaking" ~18M 7.1% A disorder that substantially impacts many people's prevalence daily lives in adults ~7M Amongst the largest mental health conditions with lifetime
36% of adults >10 years SAD prevalence affecting >31M Americans symptoms No FDA-approved fast-acting medications for as-needed Unmet medical need to large patient population treatment Advancement in care No FDA-approved fast-acting
competition Medications with the right pharmacokinetic profile and a Ability to potentially achieve large market share novel mechanism are needed Sources: US Census Bureau.
https://www.census.gov/library/stories/2021/08/united-states-adult-population-grew-faster-than-nations-total-population-from-2010-to-2020.html NIMH. Social Anxiety Disorder data from 2017 National Comorbidity Survey (NCS).
https://www.nimh.nih.gov/health/statistics/social-anxiety-disorder.shtml Anxiety and Depression Association of America (ADAA). Social Anxiety Disorder - Understand the Facts https://adaa.org/understanding-anxiety/social-anxiety-disorder
BNC210 Significantly Reduced Panic Symptoms in Humans: CCK-4-Induced
Model 9 Total # of Panic Symptoms Panic Symptom Intensity 100 100 90 90 -37.7% -52.7% Placebo- 80 80 (p<0.048) (p<0.041) 70 70 controlled study 60 60 50 50 in 15 healthy 40 40 30 volunteers who 30 20 20 experienced a 10 10 0 0 CCK-4-induced
Placebo BNC210 panic attack BNC210 demonstrated statistically significant reduction in both number and intensity of panic symptoms measured with the Panic Symptom Scale CCK-4 = Cholecystokinin Tetrapeptide (a peptide that induces anxiety and panic
symptoms) Panic Symptom Scale (% of Placebo) Panic Symptom Scale (% of Placebo)
BNC210 Phase 2 in GAD Observed to Have Acute Anxiolytic Activity 10
Performed BNC210 300 mg Fearful JORT' Faces BNC210 2000 mg Lorazepam 1.5 mg 24 GAD Patients Placebo fMRI Monitoring Significantly reduced activation of Significantly reduced connectivity Significantly reduced threat avoidance L & R
amygdala caused by viewing between amygdala and ACC while behavior of anxious subjects in the JORT fearful faces (L: p<0.05; R: p<0.01) viewing fearful faces (p<0.05) behavioral task 300 mg 300 mg Amygdala activation is an imaging
surrogate for anxiety Connectivity between the amygdala and Anterior Cingulate Cortex (ACC) is very strong in high anxiety = BNC210 Wise T. et al., Biological Psychiatry 2020 (https://doi.org/10.1016/j.biopsych.2019.12.013); Perkins A. et
al., Translational Psychiatry 2021 (https://doi.org/10.1038/s41398-020-01141-5) GAD = Generalized Anxiety Disorder JORT = Joystick Operated Runway Task fMRI = Functional Magnetic Resonance Imaging 4 WAY CROSSOVER
BNC210 Addresses the Shortcomings of Existing Social Anxiety Disorder
Approaches 11 CURRENT TREATMENTS FOR SOCIAL ANXIETY DISORDER Large Market NO NO NO FAST NO WITHDRAWAL MEMORY MOTOR Potential for Social DRUG ACTING SEDATION SYNDROME IMPAIRMENT IMPAIRMENT Anxiety Disorder 1 Benzodiazepines X X X X Attractive
Clinical Novel Mechanism 2 BNC210 & Regulatory SSRIs / SNRIs of Action Potential X X Pathway Potential for Acute Treatment in Social Anxiety Disorder Patients BNC210 IS DESIGNED TO PROVIDE ADVANTAGES COMPARED TO CURRENT THERAPIES* Anti-Anxiety
Effects NO NO NO Rapid Onset FAST In healthy subjects NO WITHDRAWAL MEMORY MOTOR DRUG ACTING SEDATION SYNDROME IMPAIRMENT IMPAIRMENT (anti-panic) and GAD of Action patients (anti-anxiety) BNC 210 * Potential benefits based on analysis of data from
separate studies and not on results that might have been obtained from head-to-head studies. Such data may not be directly comparable due to differences in study protocols, conditions and patient populations. Accordingly, cross-trial comparisons may
not be reliable predictors of the relative efficacy or other benefits of BNC210 compared to existing therapies or other product candidates that may be approved or are in development for the treatment of PTSD or SAD. 1. Includes Valium and certain
other benzodiazepines 2. Includes Prozac and certain other SSRIs (Selective Serotonin Reuptake Inhibitors) / SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)
BNC210's Rapid Onset of Action is Well-Positioned for Social
Anxiety Disorder 12 Emerging Regulatory Landscape & Unmet Need Rapid Onset of Action with BNC210 Formulation Clinically demonstrated potential for reducing anxiety in acute No fast-acting FDA-approved medications
for treatment of GAD patients and following panic induction as-needed treatment of SAD Observed acute anxiolytic efficacy of BNC210 similar to lorazepam without sedative properties and addiction liability Benzodiazepines prescribed
off-label have significant side effects of sedation, cognitive Formulation well-suited for acute dosing - Rapidly absorbed to impairment and potential for addiction high concentrations within a short period of time Growing
unmet need based on improving awareness and evolving social dynamics Maximum FDA precedent on simplified public speaking concentrations challenge endpoint for acute anxiety reduction reached in vs. placebo* ~45 - 105 min. across the
dose range *Based on path of CNS peer proceeding with registrational Phase 3 endpoint
BNC210 Phase 2 PREVAIL Social Anxiety Disorder Trial 13 Acute Social
Anxiety Disorder Study Highlights Phase 2 PREVAIL Study Design SCREENING LIEBOWITZ SOCIAL ANXIETY SCALE Potential to conduct a cost-effective trial with LSAS 70 >95: Very severe social phobia an efficacy endpoint conducive to
rapid data 80-95: Severe social phobia generation 65-80: Marked social phobia RANDOMIZATION (DOUBLE-BLIND) 55-65: Moderate social phobia Ability to leverage development strategies ~50 ~50 ~50 15 - 20 CENTERS 225 mg
675 mg of other Social Anxiety Disorder public CNS BNC 210 BNC 210 PLACEBO trial designs 60min 60min 60min EFFICACY ENDPOINT Received FDA clearance for IND filing and SUBJECTIVE UNITS OF SINGLE ANXIETY CHALLENGE DISTRESS SCALE (SUDS): FDA
Fast Track designation Measures the self-reported intensity of anxiety and/or distress in SAD patients Phase 2 trial underway and will read out topline data by end of 2022 FDA Fast Track designation Topline data expected
YE'22 LSAS = Liebowitz Social Anxiety Scale
14 BNC210 in Post-Traumatic Stress Disorder
Tackling the Profound Disease Burden of Post-Traumatic Stress Disorder
15 PTSD Represents a Significant Unmet Need 70% of people will experience a traumatic event in their lifetime, but most people recover normally ~21M 8% of adults at PTSD results from exposure to actual or threatened some point in
death, serious injury or sexual violence their lives ~9M PTSD affects up to 8% of adults during their 3.4% 1 lifetime prevalence in adults PTSD is a global mental health problem that is ~7M associated with significant morbidity and
mortality 75% of adults inadequately and shows up in all facets of peoples' lives 2 treated No newly approved pharmacotherapy in almost Unmet medical need to large patient population two decades Advancement in care No branded
competition Medications with a novel mechanism of action that Ability to potentially achieve large market share can address the pathophysiology of PTSD are needed 1. Kilpatrick, D., Resnick, H., Milanak, M., Miller, M., Keyes, K. and
Friedman, M., 2013. National Estimates of Exposure to Traumatic Events and PTSD Prevalence Using DSM-IV and DSM-5 Criteria. Journal of Traumatic Stress, 26(5), pp.537-547; 2 Mayo LM, Asratain A., Lind J et al. Elevated Anandamide,
Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial. Biol Psychiatry. 2020 Mar 15; 87(6): 538-54 2. Only 20 to 30% of PTSD
patients achieve clinical remission on SSRI therapies. US Census Bureau. https://www.census.gov/library/stories/2021/08/united-states-adult-population-grew-faster-than-nations-total-population-from-2010-to-2020.html
BNC210 Anti-Anxiety Signals Observed in Animal Models and Human
Translational Studies 16 Conditioned Fear Extinction Model Emotional Visual Analog Scale (eVAS) People with anxiety disorders and PTSD have amplified fear responses to trauma- or stress-related stimuli and impaired fear BNC210 enhanced emotional
recovery BNC210 enhanced fear extinction extinction following a CCK-induced panic attack following conditioned response training *Time in minutes after CCK-4 injection CCK-4 = Cholecystokinin Tetrapeptide (a peptide that induces anxiety and panic
symptoms) eVAS = Emotional Visual Analog Scale
BNC210 is Potentially Well-Positioned in Post-Traumatic Stress Disorder
17 Study Anti-depressant and Pharmacometric New tablet formulation Type C meeting with Phase 2b ATTUNE trial anti-anxiety trends seen analysis of Phase 2 overcomes food effect FDA started in July 2021 at
earlier time points PTSD data of suspension FDA granted Fast Track Topline data expected formulation Safety profile generally Predicted significant designation in PTSD 1H 2023 well tolerated Achieved
exposure efficacy potential with Did not meet primary target predicted from adequate drug exposure endpoint*; lower than pharmacometric achieved expected exposure of analysis liquid suspension formulation Extended IP coverage *Primary
endpoint of CAPS-5 total symptom severity score at 12 weeks
Pharmacometric Modeling Target Achieved with New Dose Solid Formulation
18 Pharmacometric (PMX) Analysis Target Exposure BNC210 Novel Spray Dry Dispersion Formulation 0 PMX modelling 300 mg Solid Dose Tablet EXPOSURE- RESPONSE CURVE on prior Phase 2 (BASELINE CAPS-5 -2 PTSD trial identified TOTAL SCORE OF 30) liquid
suspension -4 under-exposure 7-Day PK Trial BNC210 tablet New tablet formulation AUC 90 formulation -6 In-clinic 25 mg.hr/L setting -8 New formulation 0 10 20 30 40 50 60 EXPOSURE: AUC (mg.hr/L) Time (Hr) achieves target AUC >25
mg.hr/L with 900 mg dose AUC Values CAPS-5 Score Novel tablet overcomes food effect = b.i.d. (plasma exposure) (PTSD symptoms) and has dose linear exposure 7-Day Pharmacokinetic study of BNC210 tablet formulation mean AUC (mg.hr/L)
standard deviation PMX = Population pharmacometric modelling b.i.d= Administered twice daily RESPONSE ( from Placebo) BNC210 ng/ml
BNC210 Phase 2b PTSD ATTUNE Study Underway 19 WEEK 1 2 3 4 5 6 7 8 9 10
11 12 15 PHASE 2b OUTPATIENT BID DOSING FOLLOW-UP Single potential registrational- supporting trial for monotherapy Phase 2b treatment in PTSD 1:1 RANDOMIZED BNC 210 900 mg oral tablet DOUBLE-BLIND PLACEBO-CONTROLLED PLACEBO KEY INCLUSION CRITERIA
BNC210 MONOTHERAPY IN PTSD PATIENTS Female and male (18 - 75 years) ~200 Subjects Current PTSD diagnosis CAPS-5 30 (Screening & Baseline) SECONDARY ENDPOINTS PRIMARY ENDPOINT (& 25% decrease Screening to Baseline)
Various patient-reported symptoms Investigator-rated PTSD symptoms of PTSD, changes in anxiety and on CAPS-5 Total Symptom Severity ~25 Sites depression symptoms, and global Scores in change from Baseline to and social functioning; Week 12 compared
to placebo Safety & tolerability endpoints Topline data expected 1H'23 Fast Track designation from FDA BID = Twice daily dosing CAPS-5 = Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, 5th