Download SurVaxM

®
MimiVax, LLC is a spin-out company of Roswell Park Cancer Institute
formed to commercialize the SurVaxM vaccine.
Michael Ciesielski, PhD
Chief Scientific Officer,
Immunologist
Robert Fenstermaker, MD
Chief Medical Officer,
Neurosurgeon
Scott Friedman
General Counsel &
Manager,
Attorney
Out-license, acquisition by larger pharma or investment bank transaction
Phase II partnerships to bring SurVaxM through phase III & market
Inhibitor of apoptosis protein (IAP) with complex function
Expression in tumors associated with poor prognosis
Very limited expression in normal cells
Present in 95% of glioblastomas
(not a sub-population)
Present in many other cancers
C
D
4
SurVaxM
C
Molecular mimic
Enhanced MHC class I binding
Cross-reactive to wild type survivin
D
8
Long peptide
MHC class II binding – helper support
Limited HLA restriction
Multiple CD8+ T cell epitopes
Antibody responses
150%
100%
50%
0%
Survivin
SurVaxM
Mimic greatly enhances MHC-I binding (HLA-A*02)
SurVaxM stimulates a potent immune response
Immune response cross-reacts to wild type survivin in tumor cells
Epitope 5 – A*03 (1)
Epitope 4 – A*03 (1)
Epitope 3 – A*03 (1)
Epitope 1 – A*02 (4)
Epitope 2 – A*02 (6)
Epitope 6 – A*24 (1)
Epitope 7 – A*11 (1)
The long survivin peptide contained in SVN5367/M57-KLH is shown with brackets indicating
empirically confirmed reactive HLA-A*02, HLAA*03, HLA-A*11 and HLA-A*24 epitopes within
it. The position of substitution (mimic) within
the peptide is indicated (light gray).
• 9 patients with survivin-positive, recurrent malignant
gliomas and either HLA-A*02 or HLA-A*03 haplotypes.
• 4 subcutaneous injections of 500μg SurVaxM
emulsified in Montanide ISA 51 VG with
100μg of sargramostim at 2 week intervals.
• Safety & Tolerability
• Immune Response (Immunomonitoring)
• Radiographic Response (MRI)
• SurVaxM was well tolerated with minimal side effects.
Binding of MHC-peptide complexes (multimers) to CD8+ T cell receptors in patients
measured at 8 weeks through 3 years following first vaccination are shown.
2
7
1
6
3
8
2
7
5
9
3
8
Survivin antibodies produced in response to vaccination as one
activity biomarker. Seven evaluable patients produced significant
5levels (>1 O.D.) of
9 survivin-specific IgG.
100
O S : 8 e v e n ts , m e d ia n = 8 6 .6 w e e k s
P F S : 8 e v e n ts , m e d ia n = 1 7 .6 w e e k s
OS
P r o b a b ility
80
3 mo.
6 mo.
12 mo.
24 mo.
36 mo.
Median
100%
88.9%
88.9%
37.5%
25%
20.2
mos.
3 mo.
6 mo.
12 mo.
24 mo.
36 mo.
Median
50%
37.5%
37.5%
12.5%
12.5%
4.1
mos.
60
PFS
40
20
0
0
6
12
18
24
30
36
42
M o n th s
Phase I Clinical Trial: SurVaxM in recurrent glioma
Historical control median OS = 7 months; PFS6 = 14%
SurVaxM median OS = 20.2 months; PFS6 = 37.5%
•
Appears to be safe and tolerable
– Grade I injection site reactions mainly
– Fatigue, myalgia
•
Immunogenic: CD8+, CD4+ & antibodies
•
No autoimmunity observed
•
7/8 Patients OS > 12 mos.
•
2/8 Patients OS > 24 mos.
•
1/8 Patients OS > 36 mos. & CR
Immunohistochemistry of T
and B cell markers (200x) in
tissue sections of one patient
(#8) with recurrent disease 5.6
months following protocol
entry.
(A) CD4+ and (B) CD8+ T
cells in representative fields of
patient’s glioblastoma prior to
vaccine treatment, and (C)
CD4+, (D) CD8+, (E) CD20+
and (F) PD-L1+ cells within
contiguous histologic sections
of
tumor
after
vaccine
treatment and recurrence.
A
B
C
D
E
F
37 y.o. man with glioblastoma
-Surgery, XRT, TMZ
Recurrence at 5 months
-Re-resection, SurVaxM
CR, NED at 36+ mos.
6/12
Recurrence – 5 mo.
Post-op #1
8/12
Post-Op #2
9/12
On-study
7/15
34-mo Post-vax
50 patients with newly diagnosed survivin-positive glioblastoma
SurVaxM plus standard therapy
HLA-A*02, -A*03, -A*11 and -A*24
Primary: PFS6
Historical comparison well defined,
95% of all glioblastoma express survivin
Secondary: OS12, imaging, immune responses
Currently recruiting at Roswell Park and The Cleveland Clinic
and soon to be announced third national center.
18 patients with multiple myeloma receiving maintenance therapy
SurVaxM plus lenalidomide
HLA-A*02, -A*03, -A*11 and -A*24
Primary: Safety & Tolerability
Secondary: Immune response compared with added lenalidomide
Tertiary: Therapeutic efficacy, PFS
Currently recruiting at Roswell Park
2010 – 17/17 patent claims for cancer allowed by USPTO
2011 - US 7,943,138 patent “Survivin Peptides as Cancer Vaccines” awarded
2013 - patent for cancer use awarded in People’s Republic of China
2013 - patent for autoimmune diseases awarded by USPTO
2013 - patent for cancer use awarded in Japan
2014 - claim for cancer use allowed by European Union;
Validated filings: United Kingdom, Germany, France, Sweden, Spain, Italy
•
2014 - patent for cancer use awarded Hong Kong
2015 - patent for cancer use awarded Canada
2015 – patent for cancer use awarded South Korea
2007
2008
Discovery
2006
2010
2011
Pre-Clinical
2009
2013
2014
Phase I
2012
• Invention of SurVaxM peptide
• National Brain Tumor Foundation Award ($50,000)
• Patent Filed
• Completion of pre-clinical efficacy studies
• Initial meetings with FDA
• Completed FDA-mandated GMP API scale-up
• Completed GLP toxicity studies
• Patent Awarded (US)
• First IRB approval granted
• IND approved by FDA
• American Cancer Society Award ($720,000)
• Phase I clinical trial in recurrent glioma patients open
• Phase I clinical trial in recurrent glioma completed
• Private investment offering ($1.5 Million)
2015
2016
2017
Phase II
• Phase II trial in newly diag. glioblastoma patients open
• Phase I trial in multiple myeloma open
• Option/Partnership or acquisition/transaction
®
SurVaxM Immunotherapy
Michael Ciesielski, PhD
Chief Scientific Officer
[email protected]
716-845-8850