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Clinical Stage Cancer Immunotherapy
Presentation to Oxford Technology VCT AGM
August 26th 2015
Dr Richard Goodfellow: Joint CEO, Scancell
1
COMPANY PROFILE
 Focus on cancer immunotherapy
 Two cutting edge platform technologies – ImmunoBody ®and Moditope®
 Unprecedented clinical efficacy and safety on lead product SCIB1 for patients
with Stage 3/4 resected metastatic melanoma
 Deep pipeline of ImmunoBody vaccines ready for further development
 First Moditope product (Modi-1) ready to enter clinical trials in 2016
 Discussions on various options for future development of business ongoing
2
QUOTE FROM US MELANOMA SPECIALIST, AUGUST 2015
 “There is a giant hole in the management of melanoma patients and a huge
need for good adjuvant therapies”
 “Ipi (Yervoy), although effective is highly toxic. That’s why SCIB1 is so
attractive”
 “The (SCIB1) data are compelling..”
3
VALUE DRIVERS
 SCIB1 targeting adjuvant melanoma
•
•
•
•
Unparalleled survival and safety in Stage 3/4 patients
Huge untapped market
Little current or future competition for adjuvant use
Planned Phase 3 pivotal trial to secure approval based on DFS advantage
 Deep ImmunoBody® vaccine pipeline
•
•
SCIB2 targeting NY-ESO-1 ready to enter clinical trials for lung and other epithelial cancers
Flexible platform generates new candidates for further testing in weeks
 Moditope® platform offers completely novel and patented approach to T cell
stimulation. Highly effective anti-tumour effects and survival benefits in
animal studies
 Modi-1 ready to enter clinical trials, probably for triple negative breast cancer,
in late 2016
4
ACTIVE CANCER IMMUNOTHERAPY USING IMMUNOBODY®

Checkpoint inhibitors have clearly demonstrated that T cells can recognise and kill even bulky
tumours
 Most cancer vaccines have failed to deliver robust clinical results in the past as they do not
generate the HIGH AVIDITY, POTENT, T-CELL RESPONSES required for cell killing
 Scancell’s research has shown that the optimal way of producing specific high avidity T cells is by
using its DNA ImmunoBody® technology combined with electroporation (TriGrid, Ichor Medical
Systems). This approach is extending the lives of melanoma patients with minimal residual
disease following surgery
 Combining safe and effective T cell stimulation with SCIB1 with checkpoint inhibitors is a logical
approach for late stage patients
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IMMUNOBODY® T CELL ACTIVATION
 ImmunoBody® T cell activators are DNA vectors that encode engineered human antibody
molecules that target only the high affinity CD64 receptor on activated dendritic cells
 T cell epitopes are inserted into the COMPLEMENTARITY DETERMINING REGIONS [CDRs]
of the antibody framework to make a genetic antigen/antibody complex
Gene c engineering
introduces elements of
tumour-associated
an gens into the
an body structure
TUMOUR
CELL
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SCIB1 IMMUNOBODY® DESIGN
 SCIB1 ImmunoBody® incorporates epitopes from over-expressed melanoma
differentiation antigens TRP-2 and gp100, grafted into its Complementarity
Determining Regions (CDRs)
NH2
NH2
KEY:
Human constant heavy chain
Murine (de-immunized) variable heavy chain
COOH
Human constant light chain
Murine (de-immunized) variable light chain
gp100 DR4 epitope (L1 & H3)
gp100 DR7-DR53-DQ6 and nested A2 epitope (L3 & H1)
TRP-2 epitope (H2)
COOH
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SCIB1 IMMUNOBODY® DELIVERY





DNA treatment strategies are attractive because of the relative ease of manufacture and the excellent safety
profile
However, injection of DNA alone does not result in potent immune responses in humans
Electroporation generates controlled electrical pulses to create temporary pores in cell membranes and
facilitates a dramatic increase in DNA uptake; it also acts like an adjuvant and induces inflammation
SCIB1 is injected using the TriGrid electroporation device (Ichor Medical Systems)
The TriGrid 1.0 delivery system is a compact hand-held device that contains a syringe needle and four recessed
electrodes
Figur
e 2.
Electrodes
Application Cartridge
Integrated
Applicator
Injection
Needle
Pulse
Stimulator
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SCIB1 INDUCES HIGHER AVIDITY T CELLS THAN OTHER APPROACHES

SCIB1 DNA induces similar frequency responses to dendritic cells (DC) pulsed with TRP-2 peptide

However, avidity of SCIB1 DNA response is 10x higher than DC + peptide

Whole antigen DNA or peptide alone induce low frequency, low avidity responses
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SCIB1-001 STUDY DESIGN USED FOR PHASE I/II TRIAL
PHASE 1 STUDY IN PATIENTS WITH STAGE III/IV MELANOMA WITH TUMOUR PRESENT


Primary Objective – safety and tolerability
Secondary Objectives – immune responses; tumour responses
Dose escalation with safety assessment after 3 doses (0.4 mg, 2 mg, 4 mg, 8mg)
PHASE II STUDY IN PATIENTS WITH FULLY RESECTED STAGE III/IV MELANOMA


Primary Objective – safety and tolerability
Secondary Objectives – immune responses; disease free survival
STUDY SCHEDULE
 Patients dosed at Weeks 0, 3 and 6 weeks with boosts at 3 and 6 months
 Immune samples taken pre- and post-dosing
 Optional continuation phase with dosing every 3-6 months for up to 5 years
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SCIB1-001 STUDY DESIGN USED FOR PHASE I/II TRIAL
PHASE 1/2 STUDY IN PATIENTS WITH STAGE III/IV MELANOMA




Primary Objective – safety and tolerability
Secondary Objectives – immune responses; tumour responses
Part 1, cohorts 1, 2, 3 – dose escalation with safety assessment after 3 doses (0.4 mg, 2 mg, 4 mg)
Part 2, cohort 1 – resected patients at highest tolerated dose (4 mg)
No Maximum Tolerated Dose identified in Part 1; formulation improvements enabled higher dose to be evaluated…
 Part 1, cohort 4 – additional dose escalation cohort added (8 mg)
 Part 2, cohort 2 – additional patients currently being dosed at 8 mg dose
STUDY SCHEDULE
 Patients dosed at Weeks 0, 3 and 6 weeks with boosts at 3 and 6 months
 Immune samples taken pre- and post-dosing
 Optional continuation phase with dosing every 3-6 months for up to 5 years
0
Injection
with EP
3 weeks
6 weeks
3 months
6 months
3-6 months
Continuation phase
(optional)
Weeks
Immune analysis
samples
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CLINICAL SAFETY PROFILE – SCIB1 IS WELL TOLERATED

No dose-limiting toxicities observed

No adverse events (AEs) leading to discontinuation of study treatment

Vast majority of AEs were CTC grade 1 or 2

No CTC grade 4 or 5 toxicities other than those related to disease progression and one episode of
pneumonia (grade 4)

Most common AEs were transient – injection site pain, tenderness, bruising and fatigue

None of the serious AEs reported were related to study drug or study device

Electroporation causes transient pain in some patients


One patient withdrew after three doses; one declined a final injection
Study drug has been given on more than 190 occasions without any other patients withdrawing consent

Safety profile compares very favourably with several of the checkpoint inhibitors where up to 13% of
patients on pembrolizumab and 20% of patients on ipilimumab experience grade 3-5 adverse events,
predominantly autoimmune complications

Mild side effects of SCIB1 suggest treatment would be acceptable in early stage patients post-surgical
resection (adjuvant setting)
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PART 1 – TUMOUR RESPONSES AND DISEASE CONTROL
5 of 11 patients (45%) in Part 1 receiving a 2-8 mg dose of SCIB1 have shown evidence of either
an objective tumour response or disease control:
Patients with tumour present at study entry:

One patient (04-16) receiving 4 mg doses showed a “differential response” pattern in which multiple lung lesions
decreased in size or disappeared completely, whereas one abdominal wall nodule grew and was resected –
immunohistochemistry showed high levels of PD-L1 to be present

One patient (04-28) receiving 8 mg doses showed a size reduction in all lung lesions, resulting in a partial response as
defined by RECIST by Week 9 and these lesions continued to decrease in size through Week 18 and 28; two new
subcutaneous lesions developed and SCIB1 dosing ceased

A second patient (04-27) receiving 8 mg doses, with lung and breast metastases at study entry, had disease at the end of
the main study period; thereafter the breast lesion remained stable but the lung lesion increased slowly over the next 3
months
Patients with fully-resected disease at study entry:

One patient (01-24) receiving 2 mg/4 mg doses has been disease-free for 49 months having previously been treated every
year for 5 years with recurrent skin and lymph node disease

One patient (04-03) receiving 4 mg doses remained disease-free for 18 months having previously required the resection of
multiple metastases
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CT LUNG SECTIONS FROM PART 1 PATIENTS



Two patients showed objective clinical responses
CT scans showed tumour regression/disappearance
Patient 04-16 received 4 mg doses and patient 04-28 received 8 mg doses of SCIB1
Patient 04-16
(i) Pre-treatment
(ii) 9 months
Patient 04-28
(i) Pre-treatment
(ii) 6 months
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Survival of Part 2 patients with Resected Disease (4mg dose)
OVERALL SURVIVAL:
Patients with fully-resected tumour at study entry (n=16)
Overall survival (%)
100
80
60
40
20
0
0
20
40
Months since study entry
Median overall survival not reached
60
Swimmer Plot of survival of Part 2 patients with resected disease (4mg dose)
Fully-resected patients
01-24
04-03
01-34
Stage IIIA
05-08
Stage IIIB
05-09
Stage IIIC
01-37
Stage IV
01-32
SCIB1 dose (4 mg)
02-21
Disease recurrence
05-13
04-22
Follow-up
05-11
Continuing adminstration
05-19
Radiotherapy
05-21
Ipilimumab
02-33
Nivolumab
05-24
Surgery
05-18
0
5
10
15
20
25
30
Months from study entry
35
40
45
50
55
SURVIVAL AND PROGRESSION OF ALL RESECTED PATIENTS

Sixteen patients (two from Part 1 and 14 from Part 2) with fully-resected metastatic disease at study entry were recruited; nine with Stage
III and seven with Stage IV disease prior to resection

All 16 patients remain alive, with a current median observation time of 36 months (range 29-49) from study entry and only five patients
(31%) have had a recurrence of disease

Compares favourably with a peptide vaccine trial in patients with fully-resected Stage III/IV disease (Slingluff et al 2011)

Response of Stage IV patients compares favourably with a SouthWest Oncology Group study (Sosman et al 2011)
Median follow up at 36 months:
Fully resected
melanoma
patients
Survival and progression at 2 and 3 years:
SCIB1
No
Patients
Peptide vaccine
Progressed (%)
Died
(%)
Stage III/IV 1
16
31
0
Stage IV 2
7
29
0
Died
(%)
Progressed (%)
2 yr
3 yr
2 yr
3 yr
44
48
12
21
Died
(%)
2 yr
3 yr
2 yr
3 yr
77
84
53
64
et al 2011; 2Sosman et al 2011
Resected patients (n=16)
Progression-free survival (July 2015)
Disease7free-survival-(%)
1Slingluff
Progressed (%)
Untreated
Slingluff et al., 2011 J Clin Oncol 29:2924-2932
100
80
60
40
20
0
0
20
40
Months-since-study-entry
60
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SCIB1 CLINICAL TRIAL – HIGHLIGHTS

SCIB1 is safe and well tolerated

24/28 patients have developed melanoma-specific immune responses (clear dose response)
 Only one response to 0.4 mg dose – all patients progressed with a median survival of 7 months as
expected for Stage IV patients
 5/6 responded to 2/4 mg (Part 1) with a current median survival of 37 months from trial entry
 4/5 responded to 8 mg (Part 1) with a current median survival of 17 months from trial entry
 14/14 patients with resected tumour (Part 2) responded to 4 mg dose
 8 mg cohort made a 10-fold higher response than 4 mg cohort as measured by Elispot

Five of 11 (45%) patients in Part 1 receiving a 2-8 mg dose of SCIB1 have shown evidence of
a clinical response
 Reduction in tumour size or complete destruction of tumours
 Progression free survival
 Stable disease

All 16 resected patients (two in Part 1 and 14 in Part 2) are still alive (median survival 35
months) and only five have progressed
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SUMMARY OF SCIB1
 Scancell’s ImmunoBody® platform, in combination with electroporation, has set a new
standard for T cell activation
 SCIB1 shrinks and even destroys tumours in patients with inoperable metastatic melanoma
 SCIB1 prevents disease recurrence and prolongs overall survival in patients with fully
resected disease
 SCIB1 is safe and well tolerated
 Synergy of ImmunoBody® with checkpoint inhibitors in animal studies demonstrates
potential for combination use in late stage patients
 Simple and relatively inexpensive to manufacture
 Safety and efficacy profile of SCIB1 suggests future role in adjuvant melanoma – a huge and
unmet medical need
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OUR VISION FOR FUTURE IMMUNOTHERAPY OF MELANOMA
Stage *
Incidence
(%)
1A
5 year
survival (%)
Therapy
97
Surgery
IB
92
Surgery
IIA
81
Surgery, SCIB1
70
Surgery, SCIB1
IIC
53
Surgery, SCIB1
IIIA**
78
Surgery, SCIB1
59
Surgery, SCIB1, checkpoint inhibitors, BRAF inhibitors
40
Surgery, SCIB1, checkpoint inhibitors, BRAF inhibitors
67
IIB
IIIB
19
11
IIIC
IV
1
15-20
Checkpoint inhibitors
BRAF inhibitors
Tvec
CAR-T, TCR
SCIB1 combined with checkpoint inhibitors
*Stage based upon thickness of lesion, ulceration, spread to lymph nodes and spread to other organs
**The survival rate is higher for Stage IIIA cancers than for some Stage II cancers. This is likely because the main (primary) tumour is
often less advanced for IIIA cancers, although this is not clear.
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MODITOPE®
 Moditope® is a new and proprietary platform for activating the immune system against
tumour cells
 Moditope® exploits the normal immune response to stressed cells, which is largely
mediated by cytotoxic CD4+ T cells
 When normal cells are stressed or dying, they start to digest their own internal proteins
(autophagy)
 Activated enzymes modify the digested protein fragments and convert certain arginine
amino acids to citrulline
THESE MODIFIED T CELLS CAN BE HARNESSED
TO KILL TUMOUR CELLS
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MODI-1 STIMULATES POTENT ANTI-TUMOUR
RESPONSES EVEN AGAINST DAY 14 ESTABLISHED TUMOURS
 B16 tumour established in DR4 mice (Day 0)
 Single immunisation administered
on Day 4, 7, 10 or 14 (with adjuvant)
p<0.0001
p<0.0001
p<0.0001
p=0.0012
Day7 vs Day 14 p=0.016
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MODI-1 DEVELOPMENT PLAN
 On target to be ready for clinical trials in late 2016
 Development activities scheduled for 2015/2016
 Composition of Modi-1 finalised
 Peptide manufacturing
 Formulation and stability studies
 Toxicity studies
 Scientific advice meetings (MHRA/FDA)
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POTENTIAL SYNERGY BETWEEN IMMUNOBODY® AND MODITOPE®
ImmunoBody®
Moditope®
High avidity CD8+ T cell responses
Potent CD4+ T cell responses
DNA product
Peptide product
Eradicates small primary and
metastatic tumours
Eradicates large bulky tumours
Checkpoint inhibitors may enhance
responses
No requirement for checkpoint
inhibitors
Potent killer cells induced
Reverses immunosuppressive tumour
environment
Targets tumour-associated antigens
Targets modified self-antigens
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FUTURE PLANS
 Continue to strengthen and add value to SCIB1 commercial proposition
•
Continue to gather survival data , especially on cohort of 20 patients with resected disease
•
Detailed planning for a Phase 3 controlled trial in adjuvant melanoma including pre-IND meeting with
the FDA
•
Build stronger relationships with US specialists and US Patient Advocacy groups
 Development of IB pipeline and Moditope
 Continue to engage with pharma/biotech to optimise shareholder value
•
Licensing
•
M&A
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