36th Annual J.P. Morgan Healthcare Conference - January 11, 2018 - Abide Therapeutics
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36th Annual J.P. Morgan
Healthcare Conference
January 11, 2018
CONFIDENTIAL
Vision
To be the world leader in realizing
the therapeutic value of novel
serine hydrolase inhibitors to
transform the lives of patients with
serious unmet medical needs
2
Abide Therapeutics
Company
• Founded in Nov. 2011: Profs. Cravatt and
A first-in-class pipeline using Boger, Scripps Research Institute, scientific
our novel discovery platform founders. Cardinal Partners, Series A
and translational biomarkers
• Locations in Princeton and La Jolla
• ABX-1431, an oral compound, Currently 40+ employees and 35 chemists at
entering Phase 2 to treat Tourette Pharmaron (CRO, Beijing)
Syndrome and a broad range of
CNS diseases Key Events
• Three developmental compounds • Innovative discovery platform to realize
for additional CNS indications the therapeutic value of serine hydrolases
• Broad new target portfolio in
• Alliances with biotech/pharma (Celgene,
multiple therapeutic areas
Merck), and academia (Oxford, Scripps)
• Deep clinical and preclinical pipeline
backed by strong intellectual property
3
Overview:
Platform & Pipeline
CONFIDENTIAL 4
Serine Hydrolases Are a Known Biological Class That Has
Been Historically Challenging to Drug
DPP4
PNLIP AChE
The 250 enzymes in the serine hydrolase family
represent ~1% of the human genome and play
key roles in physiology and disease, yet
there are only three targets in the
superfamily with approved drugs.
We are initially focused on CNS diseases.
5
ABX-1431: First-in-Class Drug with Broad Potential in CNS
• Obsessive Compulsive Disorder Neuropsychiatric
• Agitation Disorders
• Attention Deficit Hyperactivity Disorder
• Parkinson’s Disease Movement
• Tardive Dyskinesia Disorders
• Huntington’s Disease
• Tourette Syndrome
Initial
Indication
6
Abide’s Unique Platform Focused on Serine Hydrolases
Our Pipeline Shows Its Potential
Accelerates discovery and validation of
novel disease targets in the SH superfamily
Leverages shared catalytic mechanism
unique to the entire SH enzyme family to
rapidly discover selective inhibitors from Abide’s
highly tailored library
Enables efficient translation to the clinic
• Lead molecule entering Phase 2, 3+
advancing to clinic, 20+ new targets
7
Platform Leverages Tailored Chemistry, Extensive Proteomic
and Metabolomic Profiling to Deliver First-in-Class Pipeline
In vivo ABPP:
ABPP Target Engagement Metabolomics
• Universal serine • Direct measurement of • Biochemical validation of
hydrolase activity assay in vivo enzyme inhibition new targets and inhibitors
• Rapid evaluation of • Confirmation of inhibitor • Biomarker development
inhibitor potency and selectivity; PK/PD
selectivity
First-in-Class
Drug Candidates
Serine Hydrolase Rich Source of
Superfamily
Novel Targets Abide’s Chemical Library
• >250 members • 17,000+ compounds tailored for
serine hydrolases
• Proprietary in vivo
activity atlas • Selectivity profile for every
compound 8
We are Building a Proprietary, First-in-Class Pipeline
Development Stage
Abide
Compound Target Indication Preclinical Phase 1 Phase 1b Phase 2 Rights
Tourette
MGLL CLINICAL
Syndrome
US
ABX-1431 MGLL
NMO rights
Additional
Indications
ABX-1762 MGLL CNS Disorders
PRECLINICAL
MGLL
Non-CNS Inflammatory WW
ABX-1626
MGLL Disorders rights
FAAH +
ABX-1772 Epilepsy
MGLL
TARGETS
ABD-X SH-X NASH
NEW
WW
rights
ABD-Y SH-Y Immuno-oncology
9
ABX-1431:
Lead Pipeline
Candidate
CONFIDENTIAL 10ABX-1431: Mechanism of Action
A First-in-Class, Oral, Highly-Selective MGLL Inhibitor
• Monoacylglycerol lipase (MGLL)
inhibitors regulate endocannabinoid
tone, which regulates neurotransmitter
balance
• MGLL inhibitors selectively activate CB1
by elevating 2-AG levels only in active
circuits – contrast with global, maximal,
and sustained activation by
exocannabinoids
• ABX-1431, MGLL inhibitor, has
potential for greater efficacy and
safety than exocannabinoids and can
be dosed according to medical need
11ABX-1431: Strong Foundational Studies
Preclinical Target Engagement Biomarkers Translate into the Clinic
Metabolomics ABPP PET
Desired PK/PD profile Confirms selectivity in humans Confirms target engagement in brain
and recovery of target
PN002 Subject 7 PN001 Subject 3 PN002 Subject 4
20 mg 18 mg 60 mg
12Single Dose Study of ABX-
1431 in Tourette Syndrome
CONFIDENTIAL 13Tourette Syndrome
A Disorder with Significant Unmet Medical Need
Disease Characteristics
• Neuropsychiatric disorder with childhood
onset
• Tics (involuntary, sudden, brief, repetitive
muscular movements and vocalizations)
• Premonitory urge - a substantial buildup
in tension prior to a tic
• Attention Deficit Hyperactivity Disorder
and Obsessive Compulsive Disorder are
common comorbidities amongst several
others
Tourette Association of America
14ABX-1431 Has the Potential to Address the Unmet Medical
Need in Tourette Syndrome
Physicians and patients are looking for new targeted treatments and improvements
in current treatment options, especially safety. However, drugs in development rely
on old mechanisms (e.g., Ingrezza, Austedo).
Current Treatments Unmet Needs
• Antipsychotics: Haldol, Pimozide, Abilify • Significant side effects of current treatments:
sedation, somnolence, nausea, weight
• Off label: tetrabenazine, guanfacine, clonidine, gain/metabolic effects, class risk of tardive
clonazepam, and others dyskinesia
• Comprehensive Behavioral Intervention for • 60.5% - 85% of pediatric patients estimated to
Tics (CBIT), a behavioral therapy be on psychotropic medications
• Behavioral therapies only at academic centers
15ABX-1431: Phase 1b Tourette Syndrome Trial Design
Single dose (40 mg), double blind, placebo crossover study in 20
adult TS patients.
Period 1 Period 2
ABX-1431 40 mg Placebo
Fasted
Placebo ABX-1431 40 mg
Fasted
N = 20
16Description of Clinical Endpoints for Tourette Syndrome
• Total Tic Score (TTS), FDA approval endpoint, 50 point subscale of the YGTSS
YGTSS • Clinician assessment, one-week recall (modified for 4-hour recall)
(Yale Global Tourette Severity • 25 questions related to motor tics, 25 questions related to vocal tics evaluating five domains – number,
Scale)
frequency, intensity, complexity and interference
• Patient self-assessment of tics
ATQ • Number of Unique Tics (checklist of 14 motor and 13 vocal tics), frequency and intensity of tics
(Adult Tic Questionnaire)
• Modified from one week to four hour recall
PUTS • Patient assessment of urge to tic
(Premonitory Urge to Tics • Self-reported, 9 questions (rated 1 – 4)
Scale) • Modified from one week to four hour recall
• Standardized video assessment
MRVS • Clinician assessment, of one-minute video clip graded on 5 different tic domains (rated 1 - 4),
(Modified Video Rush Scale)
maximum of 20 points
CGI-I • FDA-recommended secondary endpoint for pivotal studies
(Clinician Global Impression of • Clinician global assessment of patient improvement from baseline
Improvement) • Single assessment on 7-point scale
17ABX-1431 Phase 1b Trial Results
Single Dose Demonstrates Clear Activity on Tourette Symptoms
• ABX-1431 consistently shows positive impact on key measures of Tourette Syndrome
YGTSS (clinician interview), FDA registration endpoint
ATQ (self-assessment), effects on both motor and vocal tics
PUTS (clinician assessment), premonitory urge – limited effects observed with other drugs
CGI (clinician assessment), most accepted secondary endpoint
• ABX-1431 encouraging trends on comorbidities
Isolated cases with intriguing effects on OCD and ADHD self-assessment
• ABX-1431 well tolerated safety profile
No SAEs; most commonly observed AEs are headache, somnolence, fatigue
• Strong target engagement of MGLL with 40 mg dose
• First clinical evidence of drug effect for ABX-1431; broad potential in multiple CNS diseases
18Abilify Established Path to Approval Based on YGTSS
Initial NDA approved
ABILIFY: Primary Efficacy Datasets
Primary
Study Description N Duration Efficacy
Endpoint
KOA Phase 3 Study in South Korea* 61 10 weeks K-YGTSS 19% Decrease
21% Decrease (low dose)
293 Phase 3 Global Study 133 8 weeks YGTSS
31% Decrease (high dose)
*KOA supported registration in South Korea prior to NDA submission
19ABX-1431 Response Rates at 8 Hours Are Comparable to
Abilify at 1 Week on the FDA-Approvable Endpoint
Means of ABX-1431 vs Placebo Means of Abilify vs Placebo
Total Tic Score (SEM)
26
TTS Placebo
24 TTS Active
TTS Score
22 ~1 - 2 point
change
20
~4 point
18 change
16
0 2 4 6 8 10
Time (Hours)
At 1 week, placebo showed a
~2.5 point change and active
showed a ~6 – 7 point change
20KOLs View the Data as Significant Progress in TS
Lead Investigator Selected Other KOLs
“The treatment options for Tourette patients are limited by • “(Data) certainly is promising. “Significant” reduction. In
their efficacy profile and by CNS and metabolic safety this case, it looks like the 4-8 hour range fits with the
concerns. These ABX-1431 data are very encouraging as pharmacology. All of this looks very encouraging.
the drug was well-tolerated, and, remarkably, after only Relatively well tolerated…Reducing urges. This has all
the right stuff we want to see.”
a few hours there was a significant effect compared to
placebo. For example, one patient reported a dramatic • “Based on data, (results are) quite encouraging. Good
decrease in his urge to tic, which not only reduced the time course, very promising.”
number and intensity of his tics but also allowed him to
focus on his work. This kind of treatment effect was • “very pleased with the results… effects were very strong
for a single dose."
generally observed, suggesting that this drug has the
potential to treat all the symptoms of the disorder, unlike • “The safety profile looks good.”
current options which primarily treat only tics. ABX-1431
has the potential to be a true breakthrough in the • “The field is tired of yet another variation of existing drugs.
treatment of Tourette Syndrome.” The most compelling feature of your drug is that it is a
novel mechanism. The field hasn’t had a new
mechanism in a really long time.”
Kirsten Müller-Vahl, MD, Professor of Psychiatry at the
Department of Psychiatry, Social Psychiatry and • “There is a huge gap for a drug that won’t put you at risk
Psychotherapy at the Hannover Medical School (MHH), for tardive dyskinesia or cause weight gain and
Germany somnolence. A well-tolerated drug that decreases tics
and urge will be a no brainer.”
21Next Steps for ABX-1431:
Advance TS and Expand into Additional Indications
• Tourette Syndrome execution plan for 2018
- Begin a Phase 2 multiple-dose titration study in adults with Tourette Syndrome
- Begin a PK/PD study in adolescents
- Consult regulators in order to initiate two Phase 2b/3 pivotal pediatric studies once
acceptable safety profile established
• Select gateway indication(s) from one of the following in 2018
- Movement disorders
Chorea in Huntington’s Disease, dystonia, tardive dyskinesia
- Behavioral disorders
OCD, ADHD, aggressive behavior in autism
• Complete ongoing Phase 1b titration and neuromyelitis optica studies
22Preclinical Pipeline
CONFIDENTIAL 23Deep Expertise and Strong Chemistry Enables Desired
Endocannabinoid Modulation
MGLL Inhibitor ABX-1431 ABX-1762
Clinical Development Development Candidate
CNS Penetrant CNS disorders Additional CNS disorders
AEA 2-AG
ABX-1626
MGLL Inhibitor
Migraine
CB1,2 Peripherally
Scleroderma
Restricted Fibromyalgia
Dual MGLL/FAAH ABX-1772
Epilepsy
Inhibitor Focal seizures
CNS Penetrant Rare epilepsy syndromes
24Poised to Optimize the Potential of Serine Hydrolases
New Target Portfolio
Target Pool for Prioritization Filters for Prioritization
ABDH-A
ABHD-J ABHD-B
•Biology
•Human Genetics
•Biochemical Pathway
ABHD-C •Chemical Tools
ABHD-I •Chemical tractability
•Genetic tools Discovery
Serine Hydrolase
Superfamily •Translatability Portfolio
ABHD-D
•Competitive Landscape
•Clinical Indication
•Clinical Path
ABHD-E •Safety
•Strategic Fit
ABHD-H ABHD-F
ABHD-G
25IP & Upcoming
Milestones
CONFIDENTIAL 26Robust Intellectual Property Position
30 Patent Families Filed; 5 US Patents Issued
Joint
ABX-1431 License Internal
TSRI-Internal
Portfolio Portfolio Portfolio
Portfolio
Composition of MGLL CNS MGLL Franchise MGLL Franchise
Matter – CNS, Peripheral, CNS, Dual
– Dual –
Early Pipeline
Method of Use – Early Pipeline
– Early Pipeline
Lifecycle
Management
27Upcoming Milestones
2018 2019
1H 2H 1H 2H
Complete Phase 1b data from
Tourette Syndrome single-dose adult trial
ABX-1431
Initiate Phase 2 multiple-dose titration study
Tourette Syndrome in adults, leading to pediatric studies
Phase 1b data from multiple-
NMO dose trial
Additional Indication(s) Initiate Phase 1b study
Expect to deliver one or more compounds to the clinic in
MGLL Preclinical next 12-18 months in CNS and inflammatory disorders
Expect to select lead compounds for one or more novel targets in
New Targets next 24-36 months in various indications including: NASH and immuno-oncology
28Thank You
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