Rick Thompson findacure crdn summit 2017

1. The future of drug
repurposing for
rare diseases
Dr Rick Thompson
CEO

2. The future of drug
repurposing for
rare diseases
Dr Rick Thompson
CEO
*

3. * Personalised
medicine
Genomics
Patient
engagement
Gene editing

4. * Personalised
medicine
Genomics
Patient
engagement
Gene editing
… and
robots

5. Repurposing – Why bother?
I like my medicines new and
innovative!

7. Pricing in rare diseases
Rarity &
development
costs
Expense of
treatment

8. Pricing in rare diseases
Rarity &
development
costs
Expense of
treatment

9. At its most basic level, drug repurposing can be likened to recycling.
What is drug repurposing?
It is the act of taking a drug intended to treat one patient population, and
demonstrating its efficacy in the treatment of a completely different group
of patients.
clinical trials

10. Review of repurposing
A literature review of published examples of drug repurposing for rare diseases is
underway.
167 different cases identified so far
47 are paediatric
70 report off label use
in rare conditions
Only 3 are reported through
full clinical trials, and 4 are
retrospective analyses
11 are based on case reports
Survey question: Do you know of an example of drug repurposing in a
rare condition you represent or work in?

11. fast, cheap,
good for
rare
diseases
no
de novo
discovery
Working with what you know

12. fast, cheap,
good for
rare
diseases
no
de novo
discovery
known
safety
profile and
side effects
Working with what you know

13. fast, cheap,
good for
rare
diseases
no
de novo
discovery
known
safety
profile and
side effects
history
of human
use
Working with what you know

14. fast, cheap,
good for
rare
diseases
no
de novo
discovery
known
safety
profile and
side effects
reduced
requirement
for early stage
clinical trials
history
of human
use
Working with what you know

15. fast, cheap,
good for
rare
diseases
no
de novo
discovery
known
safety
profile and
side effects
known
pathways
of action
reduced
requirement
for early stage
clinical trials
history
of human
use
Working with what you know

16. fast, cheap,
good for
rare
diseases
no
de novo
discovery
known
safety
profile and
side effects
known
pathways
of action
reduced
requirement
for early stage
clinical trials
history
of human
use
ideas or
evidence for
repurposing
candidates
Working with what you know

17. Repurposing of generics should be appealing due to the wealth of data
available on their use in humans.
However:
Hard to secure IP on generics
Mode of use patents are hard to defend
Off-label prescription of alternative generics is hard to detect, and to prevent
Funding generic drug repurposing
Subsequently, it is more difficult for pharmaceutical companies to profit
from their development of the drug.

18. Repurposing is an ideal patient
group led collaborative model

19. Example 1: Wolfram syndrome
A rare genetic condition that affects young children from
around the age of 5.
Patients exhibit diabetes and visual impairment, which
progresses into blindness and deafness, along with other
neurological complications.
Affects about 60 people in the UK
No current approved treatment
Prof Tim Barrett has worked to secure a specialist centre
for Wolfram syndrome, and now identified a repurposing
candidate for the condition.
The first trial is starting this year.

20. Example 2: CDKL5
A rare x-linked condition
Results in early onset, difficult to control, seizures, and severe
neuro-developmental impairment
Affects about 600 people worldwide
No current approved treatment

21. Repurposing ideas - ‘Omics
‘Omics – understanding all of genes or proteins in an individual – is at the forefront of science,
and can be used to find repurposing opportunities.
normal
over
expressed
under
expressed
disease signature
Expression levels
of different genes
in a disease
affected cell

22. Repurposing ideas - ‘Omics
‘Omics – understanding all of genes or proteins in an individual – is at the forefront of science,
and can be used to find repurposing opportunities.
normal
over
expressed
under
expressed
disease signature drug signature

23. Repurposing ideas - ‘Omics
‘Omics – understanding all of genes or proteins in an individual – is at the forefront of science,
and can be used to find repurposing opportunities.
normal
over
expressed
under
expressed
disease signature drug signature therapeutic result

24. Repurposing ideas - ‘Omics
‘Omics – understanding all of genes or proteins in an individual – is at the forefront of science,
and can be used to find repurposing opportunities.
normal
over
expressed
under
expressed
disease signature drug signature therapeutic result

25. CDKL5
Data
evaluation
and curation
Develop
treatment
profile
1
month
Identified appropriate existing
datasets, treatment
requirements, and developed
disease profiles.

26. CDKL5
Data
evaluation
and curation
Develop
treatment
profile
Identify
candidate
compounds
1 3.5
month months
Identified a generic
antidepressant
that could benefit
patients
Identified appropriate existing
datasets, treatment
requirements, and developed
disease profiles.

27. CDKL5
Data
evaluation
and curation
Develop
treatment
profile
Identify
candidate
compounds
In vitro
validation
1 3.5 5
month months months
Identified a generic
antidepressant
that could benefit
patients
Showed that the
drug counter-
acted gene
silencing on
neurotransmitter
receptors
Identified appropriate existing
datasets, treatment
requirements, and developed
disease profiles.

28. Repurposing – how can we
fund this research?

29. CureAccelerator™ aims to drive more treatments to more patients more
quickly. It is an online platform to connect research funders with the
researchers who have the best repurposing ideas.
“We knew that funders had trouble finding strong, vetted repurposing research,
and researchers had no platform or funding source particularly interested in
repurposing research. It seemed natural for us to create that platform and
linkage.”
- Bruce Bloom, President and CSO, Cures Within Reach
Visit cureaccelerator.org to sign up and get involved.

30. over
1000
active
users
Visit cureaccelerator.org to sign up and get involved.

31. over
1000
active
users
Visit cureaccelerator.org to sign up and get involved.
over
20
countries

32. over
1000
active
users
Visit cureaccelerator.org to sign up and get involved.
over
20
countries
3
new funding
opportunities
posted in
January

33. over
1000
active
users
Visit cureaccelerator.org to sign up and get involved.
over
20
countries
over
130
projects
posted3
new funding
opportunities
posted in
January

34. over
1000
active
users
Visit cureaccelerator.org to sign up and get involved.
over
20
countries
over
130
projects
posted3
new funding
opportunities
posted in
January
$951,785
funding
allocated and
available

35. over
1000
active
users
Visit cureaccelerator.org to sign up and get involved.
over
20
countries
19
projects funded
in the last 16
months
over
130
projects
posted3
new funding
opportunities
posted in
January
$951,785
funding
allocated and
available

36. Rare Disease Drug Repurposing SIB
Social problem
Success measure
Intervention

37. Rare Disease Drug Repurposing SIB
Social problem
Success measure
Intervention
Large number of rare disease patients with no
treatment, and little hope of treatment. High
burden of care.

38. Rare Disease Drug Repurposing SIB
Social problem
Success measure
Intervention
Large number of rare disease patients with no
treatment, and little hope of treatment. High
burden of care.
Find generic drugs with the potential to treat
rare disease, and run clinical trials.

39. Rare Disease Drug Repurposing SIB
Social problem
Success measure
Intervention
Large number of rare disease patients with no
treatment, and little hope of treatment. High
burden of care.
Find generic drugs with the potential to treat
rare disease, and run clinical trials.
The number of rare disease patients receiving
repurposed treatments.

40. Rare Disease Drug Repurposing SIB
Social problem
Where is the money?
Success measure
Intervention
Large number of rare disease patients with no
treatment, and little hope of treatment. High
burden of care.
Find generic drugs with the potential to treat
rare disease, and run clinical trials.
The number of rare disease patients receiving
repurposed treatments.

41. Rare Disease Drug Repurposing SIB
Social problem
Where is the money?
Success measure
Intervention
Large number of rare disease patients with no
treatment, and little hope of treatment. High
burden of care.
Find generic drugs with the potential to treat
rare disease, and run clinical trials.
The number of rare disease patients receiving
repurposed treatments.
A reduced burden of care.

42. Social Impact
Bond
£ Investment
1
Investors
Repurposing at

43. Phase II
clinical trials
Social Impact
Bond
£ Investment
1
£2
Investors
Repurposing at

44. Phase II
clinical trials
Social Impact
Bond
£ Investment
1
£2
Successful trials →
new treatments
and £ savings
3
Investors
Repurposing at

45. Phase II
clinical trials
Social Impact
Bond
£ Investment
1
£2
Successful trials →
new treatments
and £ savings
3
£ % of savings
4Investors
Repurposing at

46. Phase II
clinical trials
Investors
Social Impact
Bond
£ Investment
1
£2
Successful trials →
new treatments
and £ savings
3
£ % of savings
4
£ Return on
Investment
5
6
Repurposing at

47. Phase II
clinical trials
Investors
Social Impact
Bond
£ Investment
1
£2
Successful trials →
new treatments
and £ savings
3
£ % of savings
4
£ Return on
Investment
5
6
Repurposing at
generate
returns from
healthcare
savings

48. Proving the concept
We needed to present evidence on four major areas to the
NHS and investors:
1. There is a high patient need for treatments
2. There are a number of viable generic drug repurposing
projects out there for rare diseases that lack funding
3. Show that untreated rare diseases have a high cost to
the NHS now
4. Show that repurposed generic drugs could save the NHS
money through improving patient health
Reports available online
www.findacure.org.uk/focus-groups-2016
Health
Economic
Models

49. Overall results
Congenital
hyperinsulinism
Wolfram syndrome
Friedreich’s ataxia
Cost of Illness
(per annum)
Budget Impact
(per 5 years)
A SIB can work as a tool to fund phase II proof of concept clinical trials into repurposed generic
medicines for rare diseases.
Our current examples are not the most lucrative, but the principle is sound.
£4,561,827.58 £477,693.12
£990,588.45 £672,772
£7,560,471.81 £1,148,493.99

50. Rare Repurposing Open Call
The call, hosted online by CureAccelerator™, was open to ideas from clinicians, researchers,
and patient groups worldwide. It aimed to raise the profile of drug repurposing in the rare
disease community, find new research projects for Findacure’s innovative Social Impact
Bond, and connect projects with funders and professionals with the skills to move them to
the clinic.
Do you know of a drug repurposing project for a rare disease that is
struggling to reach the clinic?
End of February to end of June 2017

51. Open Call Results
38 different proposals
Including for some better known
conditions such as:
cystic fibrosis
sickle cell anaemia
Duchenne muscular dystrophy
Excitingly, many ultra-rare conditions
were also represented, including:
epidermolysis bullosa
adult polyglucosan body disease
PTEN syndrome
5 now shortlisted for further
investigation

52. Next step?
Get the NHS on board

53. Traditional drug discovery routes cannot deliver for rare diseases. On
their own.
Repurposing offers a quicker, cheaper, and small scale collaborative
route to development of effective treatments.
Academic and patient led collaborations are proving successful.
New technologies are available to identify repurposing opportunities.
New ways to fund this research are being developed, with the aim of
delivering lower cost treatments to patients.
Summary – repurposing IS the future

54. How can patient groups get involved?
Patient group
workshops
Peer mentoring
Online portal
&
webinars