SurVaxM Cancer Immunotherapy ® SurVaxM Cancer Immunotherapy

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

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

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

SurVaxm (The Vaccine) SurVaxM Molecular mimic Long peptide 4 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

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

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).

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.

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.

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.

Phase I: Patient Response OS 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%

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

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

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

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.

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

SurVaxM Worldwide IP 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

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

SurVaxM Immunotherapy ® SurVaxM Immunotherapy Michael Ciesielski, PhD Chief Scientific Officer mciesielski@mimivax.com 716-845-8850