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CONFIDENTIAL | © COMPASS Pathways 20182 CONFIDENTIAL | © COMPASS Pathways 2018
Psilocybin
Produces a range of effects on cognition, emotions,
perception and sense of self
Mechanism of action believed to be mainly due
to 5HT2A agonism
Researched in the 1950’s but for treatment of depression, addiction,
and end of life anxiety, then became schedule I drug and research was halted
Recent surge of interest over the past 20 years. Several studies were conducted
investigating its effects on the brain, and it’s potential uses for depression,
addictions, and end-of-life anxiety in terminally ill cancer patients
COMPASS have synthetised Psilocybin to GMP standards.
CH3
OH
P
OO
H3C
N
NH
Psilocybin
NH
OH
N
H3C
Psilocin
CH3
CONFIDENTIAL | © COMPASS Pathways 2018Source: 3
'11
'16
'16
'16
U. California Los Angeles
Grob et al, 2011Archives of General
Psychiatry
NYURoss et al, 2016
Journal of Psychopharmacology
John Hopkins University Griffiths
et al, 2016Journal of
Psychopharmacology
Imperial College LondonCarhart-Harris et al,
2016The Lancet Psychiatry
Cancer-related psychological distress: Feasibility & safety for cancer patients
N=12
BDI* showed significant improvement in mood at 6 months
STAI* showed significant reduction in anxiety at 1, 3, and 6 months
Cancer-related depression: proof of concept
N=51 patients
BDI* showed significant improvement at 1, 3, 6 months
92% maintained response at 5 weeks, 79% at 6 months
Safety and efficacy of psilocybin TRD: Preliminary support for safety & efficacy
N=12
Median of 4 failed treatments, mean duration of illness of 18 years
63% of patients with response at 1 week, 47% at 5 weeks, 32% no need for further medication or therapy at 1 year
Cancer-related depression: proof of concept
N=29
BDI* showed significant improvement at 2 and 8 months
60-80% of patients maintained response at 6 months
“The use of psilocybin in treatment of
clinically diagnosed anxiety and
depression would be of substantial
interest in the NHS context,
particularly for patients with greatest
unmet need for effective clinical
interventions, e.g treatment-resistant depression.” NICE , EMA-HTA Parallel
Scientific Advice, October 2017
Psilocybin signals of efficacy
4 CONFIDENTIAL | © COMPASS Pathways 2018
The use of psilocybin in treatment of clinically diagnosed anxiety and
depression would be of substantial interest in the NHS context, particularly
for patients with greatest unmet need for effective clinical interventions,
e.g treatment-resistant depression.”NICE , EMA-HTA Parallel Scientific Advice, October 2017
5 CONFIDENTIAL | © COMPASS Pathways 2018
COMP001The Safety and Efficacy of Psilocybin In Participants with
Treatment Resistant Depression (P-TRD)
Prepared by Dr Mourad Wahba, Newcastle site 101
Supervised by Prof Hamish McAllister Williams, Newcastle site 101
CONFIDENTIAL | © COMPASS Pathways 20186 CONFIDENTIAL | © COMPASS Pathways 2018
Confirmed site Country with
confirmed site
The Study
Multicentre randomised double
blind study
Phase 2b – dose-finding
CONFIDENTIAL | © COMPASS Pathways 20187 CONFIDENTIAL | © COMPASS Pathways 2018
Confirmed site Country with
confirmed site
The Study
Oslo Helsinki
GroningenBerlin
Utrecht Prague
Mannheim
Lisbon
Barcelona
Multicentre randomised double
blind study
Phase 2b – dose-finding
17 sites in Europe,
US and Canada
Alborg
London
Manchester
Newcastle
Dublin
Study Outline
8
Weekly visits (V1a, V1b, etc)
Screening
(V1)
D -1: Baseline
(V2)D1 (V4)
Week 3
(V7)
Week 12
(EOS, V10)D0: Psilocybin
Session (V3)
72 Subjects
25 mg Psilocybin
72 Subjects
10 mg Psilocybin
72 Subjects
1 mg Psilocybin
RANDOMISATION 1:1:1
≥ 3 weeks < 6 weeks D0 D1 Week 3
Week 6 (V8)
Remote visit
Week 9 (V9)
Remote visit
Week 12
Week 1 (V5)Week 2
(V6)
Week 1 Week 2
CONFIDENTIAL | © COMPASS Pathways 2018
The aim is to allow a unique often profound subjective experience to unfold through self-directed inquiryand experiential processing
Treatment concept
Session is supported by a specially
trained therapist and a chaperone
Treatment room are designed for non-clinical
calming environment
9 CONFIDENTIAL | © COMPASS Pathways 2018
CONFIDENTIAL | © COMPASS Pathways 2018
The aim is to allow a unique often profound subjective experience to unfold through self-directed inquiryand experiential processing
Treatment concept
Patients listen to specially designed music playlist that follows
pharmacokinetics of psilocybin through high-fidelity sound system
As a result of the session, patients often experience sense of
connectedness, emotional catharsis and acceptance and gain new
perspectives
10 CONFIDENTIAL | © COMPASS Pathways 2018
CONFIDENTIAL | © COMPASS Pathways 201811 CONFIDENTIAL | © COMPASS Pathways 2018
Adverse Events of Special Interest
Transient anxiety
Nausea
Headache
Transient rise in systolic blood pressure
Transient tachycardia
Transient paranoid ideation
Transient physical discomfort
Mydriasis
Change in mood
Derealisation, depersonalization
Dizziness, fatigue
Inclusion criteria
Have successfully discontinued all serotonergic medications at least 2 weeks prior to
dosing.
McLean Screening Instrument for Borderline Personality Disorder < 7.
Failure to respond to an adequate dose and duration of 2, 3,
or 4 pharmacological treatment for the current episode. Failure includes inadequate
response to an adequate duration and dose or failure to reach an adequate dose and
duration due to lack of tolerance. Augmentation with an add-on treatment counts as a
second treatment.
Ability to complete all protocol required assessment tools without any assistance or
alteration to the copyrighted assessments, and to comply with all study visits.
18 years or older at screening
At least moderate MDD (single or recurrent episode as defined based on medical
records and clinical assessment
HAM-D 17 item score 18 or over at screening and baseline
Single or recurrent episode of depression - if single
then > 3 months, < 2 years
Signed ICF.
12
CONFIDENTIAL | © COMPASS Pathways 2018
General Medical
Psychiatric
6 CONFIDENTIAL | © COMPASS Pathways 2018
Exclusion criteria Current or past history of schizophrenia, psychotic disorder
(unless substance induced or due to a medical condition),
bipolar disorder, delusional disorder, paranoid personality
disorder, schizoaffective disorder, or borderline personality
disorder.
Prior electroconvulsive therapy and/or intravenous ketamine
for current episode.
Current cognitive behavioural therapy (CBT) that will not
remain stable for the duration of the study. CBT cannot be
initiated within 21 days of baseline.
Current (< 1 year) alcohol or drug abuse.
Significant risk of suicide. Or, if active suicidal activity or
ideation during the current episode, eligibility will be
determined at the investigator’s discretion in conjunction with
the medical monitor.
Depression secondary to other severe medical conditions.
Other personal circumstances and behaviour judged to be
incompatible with establishment of rapport or safe exposure
to psilocybin.
CONFIDENTIAL | © COMPASS Pathways 2018
Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of child bearing potential must have a negative urine pregnancy test.
Cardiovascular conditions: recent stroke (< 1 year from signing of ICF), recent myocardial infarction (< 1 year from signing of ICF), uncontrolled hypertension (blood pressure > 140/90 mmHg) or clinically significant arrhythmia within1 year of signing the ICF.
Uncontrolled OR insulin-dependent diabetes.
Seizure disorder.
Positive urine drug screen for illicit drugs or drugs of abuse. Any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator’s discretion in conjunction with the medical monitor.
Current enrolment in any investigational drug or device study or participation in such within 30 days of Screening.
Current enrolment in an interventional study for depression or participation in such within 30 days of Screening.
Abnormal and clinically significant results on the physical
General Medical
Psychiatric
Exclusion criteria
CONFIDENTIAL | © COMPASS Pathways 20187
CONFIDENTIAL | © COMPASS Pathways 2018
NHS permissions in place open to recruitment in NTW end NOV 2018 – Open to PIC sites in primary care
Source: 15
Source Referred Screened Enrolled
Secondary care 12 3 2
Primary care 6 3 0
Total 18 6 2
Referral
source
Team Number Excluded Prescreened Screened Enrolled
Secondary
care
1 3 2 2 1 1
2 1 1 1 0 0
3 3 3 2 0 0
4 1 0 1 1 Passed and titrating
5 2 2 2 0 0
6 1 1 1 0 0
7 1 1 1 1 0
Primary care Partner
organisation
3 3 3 3 0
GP group 1 1 0 1 0 0
GP 2 1 1 0 0 0
GP 3 1 0 0 0 0
CONFIDENTIAL | © COMPASS Pathways 2018
Referral Process
• Patient gives permission to be contacted by research nurse
• Patient contact details sent to study team
• Study coordinator goes through salient points of PIS over phone with patient
• If interested then medication history and medical summary required from casenotes/G.P. – referral form as much as possible populated would be helpful
• Screening visit arranged
CONFIDENTIAL | © COMPASS Pathways 2018
Contact for Referrals
• Wendy Hall (Research Nurse) study coordinator
0191 2081362 mobile 07775 997467
[email protected] (for patient identifiable information)
• Dr Mourad Wahba (Sub Investigator)
Wahba, Mourad [email protected]