Biotech Showcase January 2017 - Bionomics
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Biotech Showcase January 2017
Safe Harbor Statement
Factors Affecting Future Performance
This presentation contains "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 and BNC101), 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 funding arrangements, 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, our inability to integrate acquired businesses and technologies into our existing
business and to our competitive advantage, 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.
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.
2
Bionomics Overview
• Global, clinical stage biopharmaceutical company leveraging proprietary platform technologies to
discover and develop a deep pipeline of novel drug candidates focused on the treatment of serious
central nervous system disorders and on the treatment of cancer.
• Partnerships with Merck & Co. in cognition and pain - up to US$658m combined future potential
milestones plus additional royalties on net sales of licensed drugs
– Merck & Co equity investment in October 2015, 4.5% ownership
• Lead drug, BNC210, is a novel, orally-administered, first-in-class, modulator of α7 nicotinic
acetylcholine receptor, in development for the treatment of anxiety and depression
– Positive top line in Phase 2 clinical trial in Generalized Anxiety Disorder (GAD) patients reported
21 September 2016
– Phase 2 trial in Post Traumatic Stress Disorder (PTSD) ongoing
• BNC101 is a first-in-class anti-LGR5 antibody targeting cancer stem cells, in development for the
treatment on colon cancer and other solid tumours
– Ongoing Phase 1 trial in colon cancer patients
• BNC105 in development for the treatment of both solid and blood cancers
– Novartis funding biomarker study in renal cancer
– Investigator Initiated clinical trial in patients with Chronic Lymphocytic Leukemia will commence
in 2017
• Financials: Market Cap A$175M (29 November 2016), Cash at 30 June A$45.4M, Revenue and other
income A$21.73M, Operating loss after tax A$16.61M (30 June 2016)
3
Our Proprietary Platform Technologies
Focused on
ionX discovery of drug CSCRx
candidates for CNS
Identifies drug
candidates targeting both disorders and Identifies drug
candidates that target
ligand gated and voltage
gated ion channels for CNS
cancer cancer stem cells
indications Enables dissection and
validation of target
Proprietary cell lines and biology
screening approaches MultiCore
Proprietary in vitro assays
Comprehensive in vivo A diversity orientated combined with in vivo
models validate target chemistry platform for the assays
biology discovery of small molecule
drug candidates
Computer aided pharmacophore
modelling
Scaffold hopping synthetic approaches
rapidly create diversity in small,
focused libraries
Parallel, differentiated chemical
series of potential
drug candidates
4
Merck Partnerships: Technical Validation
Two major partnerships with Merck & Co in pain and cognition
– up to US$658m combined future potential milestones plus
additional royalties on net sales of licensed drugs
Validates ionX and MultiCore
drug discovery platforms
PA R T N E R S H I P Value creation through strategic
partnering business model
Future success based revenue
streams & royalties
5
Platform Technologies Deliver
Broad Drug Pipeline
Drug Milestones
Indication(s) Preclinical Phase 1 Phase 2
Candidate (Calendar Year)
Central Nervous System (ionX and MultiCore)
BNC 210 Generalized anxiety disorder Positive P2 results Q3 2016
Other indications including PTSD Initiated P2 trial in PTSD H1 2016
Undisclosed ADHD, Alzheimer’s, cognition, Parkinson’s, schizophrenia
Undisclosed Chronic and neuropathic pain
Others Pain, Parkinson’s dyskinesia, epilepsy
Cancer Stem Cells (CSCRx)
BNC101 Colorectal cancer Initiated P1 trial in Q1 2016
Pancreatic cancer
Other solid tumors
Cancer Stem Cells (CSCRx and MultiCore)
MELK* Solid tumors
Others Solid tumors
Other Programs
BNC105 Solid tumors, renal, ovarian, mesothelioma
BNC420 Solid tumors, melanoma, breast
BNC164 Psoriasis, uveitis
* Maternal embryonic leucine zipper kinase
6
CONFIDENTIAL
BNC210 Overview: Novel, Best-in-Class Modulator of
α7 Nicotinic Acetylcholine Receptor
Mechanism • Negative allosteric modulator of α7 nicotinic acetylcholine receptor
of Action
• Anxiety (Generalized Anxiety Disorder or GAD & Post Traumatic Stress
Target Disorder or PTSD)
Indications
• Potential for other CNS indications
Ongoing • Phase 2 trial in GAD patients, reported positive topline data Sept 2016
Clinical Trials • Phase 2 trial in PTSD initiated Q2 2016 calendar year
• 6 completed Phase 1 trials in > 200 healthy subjects
• Demonstrated safety and tolerability, no sedation, cognitive impairment
or impaired motor co-ordination, lack of side effects; suppressed
symptoms of CCK4 induced panic; target engagement demonstrated
Completed
Clinical Trials • Phase 2 in GAD patients met co- primary endpoints; low dose BNC210
outperformed Lorazepam, measured by cerebral perfusion and degree
of amygdala activation
• Secondary endpoint met; high and low dose BNC210 outperformed
Lorazepam in an anxiety provoked behavioural task (JORT)
7
BNC210: Next Generation Drug Candidate to Treat
Anxiety & Depression
Potential Competitive Advantages of BNC210*
No withdrawal No memory No drug/drug Once-a-day
Drug No sedation Fast acting
syndrome impairment interactions dosing
BNC210
Valium and other BZD x x x x
Prozac and certain other
SSRI/SNRI x x x
Anxiety Treatments Depression Treatments
• Dominated by benzodiazepines • SSRIs and SNRIs used to treat depression and
• Associated with sedation, addiction and
anxiety
tolerance and cognitive disturbances • Modest efficacy, late onset of action,
discontinuation, changes in weight, sexual
• Not recommended for long-term treatment
dysfunction and increased thoughts of
suicide in adolescents
• Many have black box warnings
*Based on data from preclinical studies and Phase 1 clinical trials.
8
Anxiety and Depression Market
Anxiety and depression have overlapping symptoms: over 40% of those
diagnosed with depression are also diagnosed with an anxiety disorder
Anxiety Market Depression Market
• Projected to reach $18 billion globally by • Approximately 18.2 million people suffer
2020 from depression in the US
• Approximately 40 million adults suffer from • Sales of top 10 depression drugs reached
anxiety in the US a total market of $8.8bn in 2012
• Anxiety patients may have more than one • Major types of depression:
anxiety disorder – Bipolar depression
Obsessive Compulsive
Disorder – Dysthymia
19.0 2.2M – Major depression
Phobias M Generalized
6.8M Anxiety Disorder
7.7M
PTSD
Social 15.0
Anxiety
Disorder M
6.0M
Panic Disorder
9
α7 Nicotinic Acetylcholine Receptor
α7 receptor has both orthosteric • Ligand gated ion channel highly
and allosteric binding sites expressed in the brain
• Key driver of emotional and memory
responses
Orthosteric binding site
Allosteric binding site
α7
Ca2+
α7
Ca2+
α7
• Allosteric modulators have no effect
on the receptor alone and do not
α7 α7
desensitize the receptor
ACh ACh • This approach provides a mechanism
for selectively and specifically
modulating the receptor to achieve
desired outcomes
– Normalize receptor activity
• Allosteric inhibition of the α7 receptor
may reduce anxiety and depression
10BNC210 Significantly Reduced CCK4-Induced Panic
Symptoms
% Reduction in Total Number of Emotional Visual
Symptoms & Symptom Intensity Analogue Scale (eVAS)
37.7% Reduction in Total 52.7% Reduction in Emotional Visual Analogue
Symptom Score Symptom Intensity Score Scale (eVAS)
10
Panic Symptoms Scale Score
Panic Symptoms Scale Score
0
*
Score
-10
*
Placebo
-20
BNC210
5.3 3.3 9.1 4.3 0 5 10 20 30 60
Placebo BNC210 Placebo BNC210 Time (min) after CCK4 Injection
Subjects Experiencing Panic Symptoms When Treated with BNC210 Showed:
• Reduction in the number and intensity of panic symptoms compared to
placebo
• More rapid return to baseline emotional stability compared to placebo
11BNC210 Phase 1 Multiple Ascending Dose Trial: BNC210
Treatment Reduced Nicotine-induced EEG Changes
The difference between nicotine-induced EEG changes
with and without BNC210 (2,000mg)
N i c o t in e S h i f t T e s t :
C o m p a r is o n b e tw e e n D a y - 1 a n d D a y 7 fo r e a c h d o s e o n
th e d iffe r e n c e b e tw e e n th e n ic o tin e d o s e a n d 0 m g
0.2
A lp h a 2 d o u b le d iffe re n c e fo r c o n tro l
D a y 7 -D a y -1 (lo g tra n sfo rm e d d a ta )
0.0
-0 . 2
-0 . 4
NS
P=0.0014 P=0.019
-0 . 6
P=0.0009
-0 . 8
0.0 0.5 1.0 1.5 2.0
D o s e o f N ic o t in e
12BNC210 Phase 2 Trial in Generalized Anxiety Disorder
(GAD) Demonstrated Acute Anxiolytic Activity
Randomized, double-blind, placebo and Lorazepam-controlled,
4-way crossover design
BNC210
King’s College Phase 2
London Primary 24 GAD Secondary
Institute of endpoints met: patients endpoints:
Psychology,
Changes in Changes in
Psychiatry and cerebral defensive
Neuroscience perfusion Functional MRI behaviour using the
Joystick Operated
Changes in brain Runway Task
Initiated March 2015 pathways relevant
to anxiety Emotional Changes in self-
(amygdala) JORT reporting of
Faces Task
Positive results during the affective
reported performance of parameters
Q3 2016 an emotional task
BNC210 is not sedating or addictive and does not impair memory or motor co-ordination
13
All years reflect calendar years. JORT – Joystick Operated Runway Task.Primary Endpoints Achieved: BNC210 Outperformed
Lorazepam in Anxiety Provoked Task
We believe GAD patients treated with BNC210 will have reduced activity
in the amygdala during performance of an anxiety provoking task
Emotional Faces Task
• Primary Endpoint Emotional Faces Task (Hariri Faces)
• Evaluate activity in the amygdala via
Functional MRI
• Several FDA-approved anxiety drugs
reduce amygdala activation evoked by
performance of the Emotional Faces
Task
300 mg of BNC210 significantly reduced
bilateral amygdala reactivity to fearful faces
pBNC210 Suppressed Anxiety-Related Defensive Behavior in
the Joystick Operated Runway Task (JORT)
Measure of
= -
defensive behaviour Average velocity/ Average velocity/
Flight intensity force used to escape force used to escape
in trials with threat in trials with no threat
Fear or anxiety result in the expression of a range of defensive
behaviors, which are aimed at escaping from the source of danger or
motivational conflict
• BNC210 administration was associated with a significant decrease
in the intensity of threat avoidance behaviour (300mg BNC210,
p=0.007; 2,000mg BNC210, p=0.033)
• Lorazepam also decreased the intensity of threat avoidance
behaviour but did not reach significance (p=0.165)
The results of the JORT further support the anti-anxiety effect of
BNC210
15
15PTSD: Poorly Served by Current Medications
• High prevalence of PTSD worldwide and it is a condition receiving greater attention.
• Patients are not well served with current medications and there is high off-label usage with
unproven or contraindicated treatments.
• BNC210 may represent a potential opportunity to displace current therapies and expand market.
16Phase 2 Trial in Post Traumatic Stress Disorder (PTSD) Initiated in
Q2 2016 - Ongoing
Subjects • 192 PTSD Patients
• Double-blind, placebo controlled, randomized, multi-centre
Protocol • 4 arms, 1 placebo, 3 BNC210 dose level treatment arms
• 12 weeks, twice daily oral treatment
Primary • To determine whether BNC210 causes a decrease in symptoms of
Objective PTSD as measured by CAPS-5
Secondary & • To determine the effects of BNC210 on anxiety (HAM-A),
Exploratory depression (MADRS) and cognitive functions
Endpoints • Correlation of genotype and imaging pharmacodynamics markers
PTSD is a risk factor for depression, alcohol or substance abuse,
absenteeism/unemployment, homelessness, violent acts, suicidal thoughts and suicide
17Bionomics Approach to Targeting Cancer Stem Cells
• Bionomics’ CSCRx platform can identify
drugs that target cancer stem cells (CSC)
Bulk
tumour Cells
– CSC have the potential to differentiate into
all cell types within a tumour Cancer
CSC
Stem Cells
– Many drugs do not specifically target CSC
leading to tumour recurrence and
metastasis Cancer Stem
Conventional Cell Therapy
Cancer Therapy
• Wnt signaling has been implicated in
proliferation and survival of CSC
CSC
CSC
• LGR5 is a receptor that modulates Wnt tumour Relapse tumour Regression
signaling in CSCs via binding of RSPO
18BNC101 Overview: First-in-class LGR5 mAb Targeting
Cancer Stem Cells
• Allosteric disruptor of LGR5/RSPO/ZNRF3 regulatory module Wnt
Mechanism of Action signal strength
• Inhibition of cancer stem cell self-renewal and tumour initiating capacity
• A monoclonal antibody (mAb) that effectively targets LGR5 will
eliminate a key pathway for CSCs
Therapeutic Hypothesis • Targeting both CSCs and the proliferate tumour bulk will prevent or
significantly delay tumour recurrence and improve treatment outcomes
and overall survival in cancer patients
• Metastatic colorectal and pancreatic cancers
Target Indications
• Potential for other solid tumours including breast, lung, GI tract
• Single agent dose escalation/expansion in 2nd/3rd line metastatic CRC
(mCRC)
Clinical Development • Chemotherapy combination + BNC101
Plan
• Demonstration of safety and tolerability
• Exploratory Endpoints: OS, PFS, biomarkers
19Market Opportunity
Currently approved therapies do not effectively address the underlying
mechanism of tumor recurrence and metastasis
CRC Therapeutic Market Pancreatic Cancer Therapeutic Market
• Projected to reach US$9B by 2020 in 8 Major • Projected to reach US$5B by 2020 in 8 Major
Countries Countries
• Colorectal Cancer (CRC) is the second most • Pancreatic Cancer remains a high unmet need
prevalent cancer type, yet overall survival lags due to lack of safe and highly efficacious
behind other high incidence cancers products in the market
• Metastatic CRC incidence = >136,00 new cases • Pancreatic cancer incidence = 46,420 new cases
in US in 2014 in US in 2014 (38,000 deaths)
• In metastatic CRC, five year survival is just 12% • In Pancreatic Cancer, five year survival is just 6%
Additional LGR5+ Solid Tumors
• Triple negative breast cancer therapeutic market
est. US$6B by 2020
• Lung cancer therapeutic market est. US$4.5B by
2020
• Hepatocellular (liver) cancer therapeutic market
est. US$1.5B by 2020
20
Source: GBI Research - Cancer Therapeutics in Major Developed Markets to 2020BNC105 exerts direct anti-cancer efficacy through multiple
modes of action in both solid and blood borne tumours
BNC105 induced tumour vasculature destruction, tumour hypoxia and necrosis leads to
changes in the tumour microenvironment and the surrounding immune ‘landscape‘
Proposed mechanism of anti-tumour immunity
induced by BNC105
Re-awakening the immune
BNC105
system contributes to the
changes seen in the tumour
microenvironment via:
• an efflux of immune
presenting tumour
antigens via tumour
disruption/necrosis
• enhanced maturation of
dendritic cells into
antigen presenting cells
• release of pro and anti-
inflammatory cytokines
Modified from: Muller, Oncolmmunology 2014
Tubulin polymerization inhibitors (TPI) induce functional maturation of dendritic cells (Muller, OncoImmunology 2014)
TPIs program dendritic cells toward enhanced anti-tumour immunity (Martin, Cancer Immunology Immunotherapy 2014)
21Outlook & Milestones
• Continue to recruit patients into the ongoing clinical trial of BNC210 in patients with
PTSD.
– 8 sites initiated in Australia, US sites anticipated Q1, 2017
– Target complete recruitment end 2017, will update once all US sites activated
• Explore both partnership options and pathways for broader Phase 2 development of
BNC210.
• Work closely with MSD, enabling MSD to reach milestones and demonstrate Bionomics
strength in drug discovery.
– Anticipate first, significant milestone payment with imminent start of clinical trial
• Phase 1 BNC101 trial results in patients with colon cancer Q2,2017 and Q3, 2017:
– Recommended Phase 2 dose level
– Data from expanded patient cohort
• Further opportunities for BNC105 development and partnering
– Investigator – initiated clinical trial in CLL to commence early in 2017
– Novartis-funded biomarker study
• Add to our strategic partnerships
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