Toca 511= virus + CD gene

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SNI Clinical Trials
Neuro-oncology
SNI Clinical Trials
Neuro-oncology
Glioblastoma – Newly diagnosed
• Immunotherapy
- DCVax- tumor antigen pulsed dendritic cells
- Celldex- EGFR VIII mutant vaccine
• Small molecule VEGF inhibitor
- cediranib
• NovoCure TTF device
High grade glioma – Recurrence
• Retroviral gene therapy
-cytosine deaminase prodrug conversion
SNI Clinical Trials
Neuro-oncology
GBM Newly Diagnosed - Phase II
ACT IV
A Randomized, Double-Blind, Controlled Study
of Rindopepimut/GM-CSF with
Adjuvant Temozolomide in Patients with
Newly Diagnosed, Surgically Resected,
EGFRvIII-positive Glioblastoma
The EGFR Mutation Variant III (EGFRvIII)
EGF-binding
domain
Transmembrane
domain
Intracellular
domain
NH2
COOH
wtEGFR
EGFRvIII
• Tumor-specific oncogene ideally suited for immune targeting
• Expressed in 1/3 of primary glioblastoma, but not in normal tissue
• In-frame deletion of exons 2-7 results in constitutively active
protein with unique amino acid sequence at the fusion junction
• Epitope is in the extracellular domain; accessible to antibodies and
highly immunogenic
Rindopepimut (CDX-110)
Vaccine designed to generate a specific immune
response against EGFRvIII-expressing tumors
• “Off the shelf” vaccine recognized across HLA types
• Consists of the EGFRvIII antigen (unique 13 amino acid peptide
sequence) chemically conjugated to Keyhole Limpet Hemocyanin
• Delivered as intradermal injection of 500ug
rindopepimut with
150ug GM-CSF
• Stable lyophilized
formulation
O N
O
S
N
KLH
O
LEEKKGNYVVTDHC
>30
ACT IV Study Design
R
A
N
D
O
M
I
Z
A
T
I
O
N
Vaccine
Priming
Adjuvant Temozolomide and Vaccine
Therapy (TMZ-V, 6-12 cycles)
Vaccine
Maintenance
Therapy (VMT)
§
§
D1
D15
• Dose vaccine days
1 and 15 of Vaccine
Priming cycle
• Start cycle within 4
days after
randomization and
within 7-14 days
after completion of
CRT
C1D1
C1D22
C2D22
C3D22
etc….
• Vaccine or placebo is administered Day 22
of each TMZ cycle
• Begin TMZ no sooner than 6 days after
administration of the second vaccine
priming dose
• Begin TMZ no sooner than 28 days after
completion of CRT
• Begin TMZ when ANC  1000/L and
platelets  100,000/L
Follow Up
C1D1
C2D1 etc…
If no disease
progression
after TMZ,
continue dosing
vaccine every
28 days (Day 1
±3 days of each
28 day cycle)
until intolerance
or disease
progression
Follow-up for
overall survival
every 12 weeks
after disease
progression
• TMZ dosed days 1-5 of each 28 day cycle
§
CRT
Temozolomide Dosing
Vaccine or Placebo Dosing
Tumor Assessments – every twelve weeks
Chemoradiation Therapy
Treatment will be discontinued upon
disease progression, unacceptable
treatment-related toxicity, or patient
refusal to continue study treatment
SNI Clinical Trials
Neuro-oncology
GBM Newly Diagnosed - Phase II
DCVax-L
An Autologous, Dendritic Cell Based
Therapeutic Vaccine for Newly Diagnosed
Glioblastoma Multiforme
SNI Clinical Trials
Neuro-oncology
DCVax-L
Vaccine produced from:
- Autologous dendritic cells generated from PBMC
- Pulsed with autologous GBM lysate
- Subcutaneous vaccine injections
- During adjuvant TMZ
SNI Clinical Trials
Neuro-oncology
GBM Recurrence - Phase I
Tocagen 511
A Phase 1 Ascending Dose Trial of the Safety and
Tolerability of Toca 511, a Retroviral Replicating Vector,
Administered to Subjects at the Time of Resection for
Recurrent High Grade Glioma and Followed by Treatment
with Toca FC, Extended-Release 5-FC
Toca 511 delivers yeast cytosine
deaminase gene into replicating
tumor cells
U3
R U5
gag
pol
env
U3
R U5

IRES
5-FC
• 5-FC is orally available
• 5-FC crosses the BBB
CD
Cytosine Deaminase
5-FU
Infected tumor cells convert 5-FC to 5-FU
Toca 511 injected into tumor
5-FC taken orally
Toca 511
5-FC
5-FU
CD
Tumor
Normal tissue
Toca 511 spreads through tumor
Toca 511= virus + CD gene
2012 Copyright Tocagen Inc.
Tumor regression
SNI Clinical Trials
30
Translational Studies
MS
Clinical Studies
25
Brain Tumor
N = 79
20
15
Pituitary
Epilepsy
10
Spine
Cerebrovascular
5
Neuro-ophth
Movement
Disorders
Psychiatry
Stroke
0
Research Patient Enrollment
800
700
600
500
400
300
Dec-10 Jan-11 Feb-11 Mar-11 Apr-11 May-11 Jun-11
Jul-11
Aug-11 Sep-11 Oct-11 Nov-11 Dec-11 Jan-12
SNI Clinical Trials
Swedish Neuroscience Inst
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