1. SurVaxM Cancer Immunotherapy
SurVaxM
Cancer Immunotherapy

2. 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

3. Objectives
Out-license, acquisition by larger pharma or investment bank transaction
Phase II partnerships to bring SurVaxM through phase III & market

4. The Survivin Molecule as a Target
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

5. SurVaxm (The Vaccine) SurVaxM Molecular mimic Long peptide4
KLH
SurVaxM D C 8
Molecular mimic
Enhanced MHC class I binding
Cross-reactive to wild type survivin
Long peptide
MHC class II binding – helper support
Limited HLA restriction
Multiple CD8+ T cell epitopes
Antibody responses

6. SurVaxM: Enhanced Molecular Mimic
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

7. SurVaxm: Multi-Epitope Long Peptide
Epitope 2 – A*02 (6)
Epitope 1 – A*02 (4)
Epitope 3 – A*03 (1)
Epitope 6 – A*24 (1)
Epitope 4 – A*03 (1)
Epitope 5 – A*03 (1)
Epitope 7 – A*11 (1)
The long survivin peptide contained in SVN53-67/M57-KLH is shown with brackets indicating empirically confirmed reactive HLA-A*02, HLA-A*03, HLA-A*11 and HLA-A*24 epitopes within it. The position of substitution (mimic) within the peptide is indicated (light gray).

8. Phase I Clinical Trial: Recurrent Glioma: Completed
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.

9. Phase I: Immune Response - CD8+ T cells
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.

10. Phase I: Immune Response - Antibodies
Survivin antibodies produced in response to vaccination as one activity biomarker. Seven evaluable patients produced significant levels (>1 O.D.) of survivin-specific IgG.

11. Phase I: Patient ResponseOS
3 mo.
6 mo.
12 mo.
24 mo.
36 mo.
Median
100%
88.9%
37.5%
25%
20.2 mos.
PFS
3 mo.
6 mo.
12 mo.
24 mo.
36 mo.
Median
50%
37.5%
12.5%
4.1 mos.
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%

12. SurVaxM: “First in Human” Clinical Trial in recurrent Malignant Glioma
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

13. Phase I: Immune Response-Tumor Infiltrates
CD4 - Pre
CD8 - Pre
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.
CD4 - Post
CD8 - Post
CD20 - Post
PD-L1 - Post

14. Phase I: Radiographic Response
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

15. SurVaxM: Phase II - glioblastoma
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.

16. SurVaxM: Phase I – multiple myeloma
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

17. SurVaxM Worldwide IP
2010 – 17/17 patent claims for cancer allowed by USPTO
US 7,943,138 patent “Survivin Peptides as Cancer Vaccines” awarded
patent for cancer use awarded in People’s Republic of China
patent for autoimmune diseases awarded by USPTO
patent for cancer use awarded in Japan
claim for cancer use allowed by European Union;
Validated filings: United Kingdom, Germany, France, Sweden, Spain, Italy
patent for cancer use awarded Hong Kong
patent for cancer use awarded Canada
2015 – patent for cancer use awarded South Korea

18. SurVaxM Development Timeline
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
2017
Discovery
Invention of SurVaxM peptide
National Brain Tumor Foundation Award ($50,000)
Patent Filed
Completion of pre-clinical efficacy studies
Pre-Clinical
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
Phase I clinical trial in recurrent glioma patients open
Phase I clinical trial in recurrent glioma completed
Private investment offering ($1.5 Million)
Phase II trial in newly diag. glioblastoma patients open
Phase I trial in multiple myeloma open
Option/Partnership or acquisition/transaction
Phase II

19. SurVaxM Immunotherapy
SurVaxM Immunotherapy
Michael Ciesielski, PhD
Chief Scientific Officer