Using psychedelics ‐ Psilocybin · Psilocybin Produces a range of effects on cognition, emotions, perception and sense of self Mechanism of action believed to be mainly due to 5HT2A

Using psychedelics ‐ Psilocybin

Wendy Hall

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

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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


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


Confirmed site Country with

confirmed site

The Study

Multicentre randomised double

blind study

Phase 2b – dose-finding


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



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



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


General Medical

Psychiatric


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.


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



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


News updates


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


Referral Form


Contact for Referrals

• Wendy Hall (Research Nurse) study coordinator

0191 2081362 mobile 07775 997467

[email protected]

[email protected] (for patient identifiable information)

• Dr Mourad Wahba (Sub Investigator)

Wahba, Mourad [email protected]

mailto:[email protected]




•Questions

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Using psychedelics ‐ Psilocybin · Psilocybin Produces a range of effects on cognition, emotions, perception and sense of self Mechanism of action believed to be mainly due to 5HT2A