Forward Looking Statements

Transcription

1 June 2016

2 Forward Looking Statements Advaxis, Inc. (the Company ) has filed a registration statement (including a prospectus) and will file a preliminary prospectus supplement with the Securities and Exchange Commission ( SEC ) for the offering to which this presentation relates. Before you invest, you should read the prospectus and the preliminary prospectus supplement in that registration statement and other documents the Company has filed with the SEC for more complete information about the Company and the offering. This presentation contains forward-looking statements, including, but not limited to: statements regarding Advaxis' ability to develop the next generation of cancer immunotherapies; and the safety and efficacy of Advaxis' proprietary immunotherapy, axalimogene filolisbac. These forward-looking statements are subject to a number of risks, including the risk factors set forth from time to time in Advaxis's SEC filings, including but not limited to its report on Form 10-K for the fiscal year ended October 31, 2015, which is available at Advaxis undertakes no obligation to publicly release the result of any revision to these forward-looking statements, which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, except as required by law. You are cautioned not to place undue reliance on any forward-looking statements. 2

3 Advaxis Overview Background Core technology live attenuated Listeria monocytogenes (Lm) bacterial vector stimulates the immune system to view tumor cells as bacterial infected cells and subsequently targets them for elimination Alters tumor microenvironment by increasing tumor fighting cells and decreasing tumor protecting cells ~60 employees with lab, office, manufacturing facilities, and vivarium located in Princeton, NJ Financial Snapshot Raised ~$165M since October 2013 Cash: ~$94.6M as of April 30, 2016 Summary of Strengths Extremely versatile platform technology can be used to treat any type of cancer through targeting driver mutations and/or neoepitopes Existing collaborations with Merck & Co., Inc. and AstraZeneca/MedImmune, LLC Straightforward and scalable manufacturing process with low COG Highly proprietary technology (80+ patents) with low royalty obligation (2.5%) 3

4 Key Value Drivers Lm Technology Candidates in Development Axalimogene filolisbac (AXAL) Comprehensive clinical development program in early and late stage HPV-associated cancers ADXS-HER2 Clinical development program in multiple HER2-expressing solid tumors AT-014 for canine osteosarcoma anticipated launch in 2016 (licensed to Aratana/NASDAQ: PETX) ADXS-PSA Clinical development program in metastatic castration-resistant prostate cancer (mcrpc) as monotherapy and in combination with KEYTRUDA Orphan Drug Designations for invasive cervical cancer, head and neck cancer, anal cancer, and osteosarcoma Preclinical Pipeline ADXS-NEO Neoepitope-based immunotherapy targeting mutations identified in an individual patient s tumor using massive parallel sequencing; IND anticipated 2016 ADXS-TNBC Triple negative breast cancer; IND anticipated 2016 Combination with Other Cancer Therapies Synergistic response with checkpoint inhibitors (PD-1 and PD-L1) and costimulatory molecules (OX40 and GITR) in preclinical models Enhanced response in combination with radiation in preclinical prostate cancer models KEYTRUDA is a registered trademark of Merck & Co., Inc. 4

5 Inside Advaxis ASCO Booth 5

6 Lm Technology Overview: Harnessing Unique Life Cycle of Lm in APCs Lm-LLO and Tumor Associated Antigen (TAA) presented and taken up by dendritic cells (antigen presenting cells or APCs) 2 Some Lm-LLO is killed and degraded within the phagolysosome Dendritic cells activated to generate an immune response through both the MHC I and MHC II pathways Robust T-cell response generated toward antigen secreted by Lm-LLO and redirected against tumors expressing the same TAA "Perceived" acute infection stimulates a strong innate immune response through multiple pathways (e.g. STING) Over-rides checkpoint inhibitors and negative regulators of cellular immunity 1 Lm-LLO is phagocytosed by APC 3 Some Lm-LLO escapes the phagolysosome and enters the cytosol 4 tllo-taa fusion protein is degraded by proteasomes into peptides for presentation to the MHC class I pathway 5 Peptide-MHC complexes on the APC simulate CD4+ (MHC II) and CD8+ (MHC I) T-cells APC, antigen presenting cell; Lm, Listeria monocytogenes; MHC, major histocompatibility complex; TAA, tumor-associated antigen; tllo, truncated listeriolysin O 6

7 Targeting Neoepitopes Is the Next Step in the Evolution of Cancer Immunotherapy Why does cancer develop neoepitopes? Tumors develop because of mutations in genes coding for key regulatory and functional proteins Expression of mutated proteins causes aberrant cellular functions that result in malignancy, and malignant cells survive by avoiding the immune system Normal peptides are weakly immunogenic (central tolerance deletes high avidity clones), but mutated cancer proteins are completely different from normal cells (neoepitopes) How can this be used to attack cancer? Immunotherapies work by activating the patient s immune system to target epitopes in cancer cells High avidity cytotoxic T-cells can be generated against neoepitopes Checkpoint inhibition appears to work by enabling pre-existing T cells to respond against neoepitopes, expand, and become tumoricidal Immunizing patients against their own neoepitopes with an attenuated live vector will generate or enhance T-cell responses against neoepitopes Because the T cell responses are only directed against the mutated neoepitopes, and there is no systemic blockade of tolerance, there should be no off-target toxicity and few AEs 7

8 Targeting Neoepitopes with Lm Technology Advantages for Personalized Immunotherapy Lm Technology has advantages for targeting neoepitopes Bandwidth for example, 5 constructs can present >250 tumor neoepitopes to T-cells, obviating the need for a predictive algorithm Feasibility affordable and easy to manufacture intime for patient treatment (compare to autologous therapy) tllo TAA fusion protein is a synthetic peptide presenting multiple neoepitopes secreted into the cytoplasm of the APC plasmid copies per bacteria Payload for neoepitopes per construct up to ~2k+ amino acids Multiple constructs can be administered for larger numbers of neoepitopes Activates other immune pathways (TLRs, PAMP, STING, DAMP, NOD1, NOD2, CpG) Treatments can be given repeatedly without neutralizing antibodies Generates strong innate and adaptive T cell response, even to lower avidity epitopes Decreases Tregs and MDSCs in the tumor microenvironment TAA, tumor-associated antigen 8

9 ADXS-NEO Start to Finish How does it work? Academic or Commercial Massively Parallel Sequencing Advaxis Immunotherapies Patient s Hospital or Treating Institution Sequencing to identify nonsynonymous mutations Advaxis designs vector based on neoepitopes Treat patient with personalized immunotherapy vector based on his/her neoepitopes Identify neoepitopes DNA synthesis molecular cloning into plasmids Multiple cycles of treatment and combination with RT, PD-1, co-stims possible Transfection into personalized vector, QA/QC OK Ship to patient s institution Time from biopsy to infusion administration = ~6 weeks 9

10 ADXS-NEO: Next Steps Pre-IND meeting completed Planning to file IND in 2016 Continue building collaborations to drive ADXS-NEO forward as rapidly as possible MINE Collaboration with Memorial Sloan Kettering Cancer Center will focus on preclinical and clinical development of neoepitope-based Lm treatments Completion of in-house manufacturing facility in 2016 to enable clinical supply 10

11 Axalimogene Filolisbac: Open Label 2-Stage Phase 2 Study In Recurrent Cervical Cancer (GOG 0265) PRIMARY EFFICACY ENDPOINT: 12-MONTH SURVIVAL Tewari KS, Monk BJ. CurrOncolRep. 2005; 7(6):419-34; GOG, Gynecologic Oncology Group 11

12 29 ENROLLED Axalimogene Filolisbac: Open Label 2-Stage Phase 2 Study In Recurrent Cervical Cancer (GOG 0265) Stage 1 Data Presented at American Gynecological & Obstetrical Society (AGOS) did not receive therapy 26 treated 10 patients achieved required 12-month survival 12-month survival rate = 38.5% Study exceeded required 20.0% efficacy threshold and predetermined safety criteria and has proceeded to Stage 2 with additional enrollment of 37 patients No approved therapy following failure of first-line treatment, with historical survival only 4-7 months 1 Safety Summary: Axalimogene filolisbac was well-tolerated, with Grade 1-2 fatigue, chills, and fever the most commonly reported AEs; six patients experienced a treatment-related Grade 3 or Grade 4 AE, which was considered possibly related to axalimogene filolisbac. The adverse events observed in the first stage of the study have been consistent with those reported in other clinical trials with axalimogene filolisbac. 1 Monk BJ, et al. J Clin Oncol. 2009;27(7): Presented by Thomas Herzog, MD, at AGOS

13 GOG 0265: Stage 1 Final Data Overall Survival Among 18 (69%) patients who received all 3 per-protocol doses, median OS exceeded 1 year (12.1 months) and 12-month survival was 55.6% Presented by Thomas Herzog, MD, at AGOS

14 127B 127C 127D 127F 127H 127K 127L 127N1 127N2 127P 127Q 127R 127S 127T 127U 227C 227D 265 Isotretinoin + IFNα Cisplatin + penoxifyline Altretamine Topotecan Etoposide Gemcitabine Vinorelbine Bryostatin-I (dose 1) Bryostatin-I (dose 2) Oxaliplatin Cisplatin + gemcitabine Liposomal doxorubicin Docetaxel Pemetrexed Weekly topotecan Erlotinib 12-month survival rate* Axalimogene filolisbac (Stage I) Bevacizumab GOG 0265 Clinical Significance GOG has conducted numerous Phase 2, single-arm, two stage studies in recurrent persistent recurrent/metastatic cervical cancer The 12-month OS rate has never exceeded 30% In stage 1 of Study 0265 (n=10), 12- month OS was 38.5%, exceeding historical rates in this difficult to treat population GOG 0265 included a more heavily pretreated population than previous trials and included post-progression CT and bevacizumab-treated patients AXAL showed activity against recurrent cervical cancer with and without standard chemotherapy 3 doses of AXAL as monotherapy produced CRs in a difficult to treat patient population with few treatment options Historical Perspective of 12-month Survival in GOG P2 Trials for Recurrent/Metastatic Cervical Cancer 40% 35% 30% 25% 20% 15% 10% 5% 0% # Prior regimens GOG Study and Publication Date Presented by Thomas Herzog, MD, at AGOS 2015 AXAL Axalimogene filolisbac *Derived from product limit estimate of probability of surviving >12 months 14

15 GOG 0265: Stage 2 Results Survival Benefits are Consistent with Stage 1 Results Findings from Stage 2 Suggest Consistent Survival Benefit All Patients (N = 24) 6-month OS 42% (n = 10/24) >3 Doses of ADXS (N = 12) 67% (n = 8/12) Median OS (95% CI) Median PFS (95% CI) 4.8 months (3.8 NR) 2.6 months ( ) NR (3.5 NR) - CR 1 (4) - Tumor Response SD 8 (33) - PD 11 (46) - NE 4 (17) - Median PFS of 2.6 months was similar to that observed in Stage 1, although 10/24 (42%) patients discontinued ADXS without progression or death due to clinical hold The primary endpoint of 12-month survival rate could not be calculated due to limited median follow-up of 8.7 months Safety findings in Stage 2 patients were similar to Stage 1 Prior lines of systemic-dose therapy n (%) 14 (58) 10 (42) 0 (0) Prior bevacizumab, n (%) 20 (83) Prior pelvic radiation, n (%) 22 (92) CR, complete response, NE, no evaluation; PD, progressive disease, SD, stable disease. Presented by Warner Huh, MD, at ASCO

16 GOG 0265: Stage 2 Results Complete Response Case Study Patient Overview 66-year-old woman diagnosed with squamous cell cancer of the cervix in 2006, surgically treated with radical hysterectomy in 2007 Pelvic recurrence in 2014 Paclitaxel/carboplatin 8 cycles (6 cycles with bevacizumab) cisplatin (2 cycles) + pelvic radiation. Treatment completed August 2014 Systemic recurrence June 2015 Enrolled in GOG/NRG Month Survival To Date, Complete Tumor Response Second-line metastatic squamous cell cervical cancer (post-bevacizumab) ADXS well tolerated Application for Individual Patient IND for ADXS ONGOING GOG/NRG-0265 ADXS Dose 1 GOG/NRG-0265 ADXS Dose 2 GOG/NRG-0265 ADXS Dose 3 CT Scan PR (>30% ) CT Scan Confirmed PR with further PET/CT Scan NED - CR PET/CT Scan NED - CR ADXS Clinical Hold Oct 2015 Dec 2015 Jan 2016 May 2016 July 2015 Aug 2015 Sep 2015 CR, complete response; CT, computed tomography; GOG, Gynecologic Oncology Group; IND, Investigational New Drug; NED, no evidence of disease; PET, positron emission tomography; PR, partial response. Presented by Warner Huh, MD, at ASCO

17 GOG 0265: Stage 2 Results Complete Response Case Study Evidence of Durable Complete Response Presented by Warner Huh, MD, at ASCO

18 Axalimogene Filolisbac: Next Steps Phase 3 AIM2CERV Study Schema RANDOMIZATION 1:2 BETWEEN REFERENCE AND TREATMENT GROUPS 18

19 Axalimogene Filolisbac + Mitomycin, 5-FU, & Radiation Open Label Phase 1/2 Study Anal Cancer (BrUOG*) PRIMARY EFFICACY ENDPOINT: 6-MONTH CR-RATE Axalimogene Filolisbac 1x10 9 cfu x 4 (1 prior to chemort and 3 post, q 28 days) as a 500 ml infusion over 30 min N = 25 Primary stage II-III anal cancer High risk of recurrence HPV-positive BIOPSY Axalimogene filolisbac #1 Day -10 to 14 6 WEEKS 28 DAYS 28 DAYS 6 weeks IMRT Axalimogene filolisbac #2 Day +10 post IMRT Axalimogene filolisbac #3 BIOPSY Follow up Axalimogene filolisbac #4 Primary efficacy endpoint is 6-month CR-Rate, defined as the rate of clinical complete response as determined by evaluation by proctoscopy at 6-months post-treatment *BrUOG, Brown University Oncology Group; Perez K et al. IANS 2015; Abstract 23 19

20 Axalimogene Filolisbac + Mitomycin, 5-FU, & Radiation Phase 1/2 Anal Cancer Study (BrUOG) Preliminary Data Study open: April 2013 Accrual: N = 10 / 25 enrolled Efficacy Summary: All patients who have completed treatment achieved CR (N = 9) No evidence of recurrence Historical 3-year recurrence rate in similar patient population = ~45% Follow-up duration: 0.5 months 33 months Safety Summary: Did not worsen the toxicity profile of standard chemoradiation Chills, occasional rigors and flulike symptoms resolved prior to leaving clinic (~2 hours) TNM stage T4N3 11 T3N0 10 T3N0 9 T3N3 8 T2N0 7 T4N0 6 T3N3 5 T4N0 4 T2N2 3 T3N3 2 *As of Jan 6, 2016 Relapse Free Survival (RFS) Follow-up duration months N = 10 treatment patients Patient progressed systemically Patient expired unrelated to study treatment Relapse Free Survival (Days)* Note: Patient #1 enrolled but was never treated on study On ADXS RFS Hx 3-yr RFS in stage-matched population ~45% Perez K et al. IANS 2015; Abstract

21 Axalimogene Filolisbac + PD-L1/PD-1 Initial Phase 2/3 Study in Anal Cancer: FAWCETT 21

22 Percent Survival Preclinical Rationale for Checkpoint Combination Trials AXAL + PD-1 HPV Tumor Model TC-1 tumor implantation Tx 1 Tx Days 15 Treatments: Lm-LLO-E7: CT-011 mab: 5x10 6 cfu 50 μg Days after tumor implantation Lm immunotherapy is synergistic with checkpoint inhibitors Data from Mkrtichyan M, et al. J Immunother Cancer 2013, 1:15 doi: /

23 Combination with anti-pd-l1 (durvalumab) Metastatic Cervical Cancer or Head & Neck Cancer 23

24 ADXS-PSA: Phase 1/2 Dose Escalation and Safety Study Alone and Combined with PD-1 (Keytruda ) 24

25 ADXS-HER2 Phase 1 Study in Canine Osteosarcoma: Safety & Efficacy # Dogs with Treatment Related Adverse Events (All toxicities reported are Grade 1) ADXS-HER2 Dose 2x10 8 5x10 8 1x10 9 3x10 9 Total Number of dogs recruited N=3 N=3 N=9 N=3 N=18 General Disorders Pyrexia (>103) Fatigue GI Disorders Vomiting Nausea Cardiovascular Arrhythmias Tachycardia Hypotension Hematological parameters Thrombocytopenia Biochemical parameters (increase) γ-gt Alkaline Phosphatase ALT AST BUN CREA Cardiac Troponin I ADXS-HER2 and Overall Survival p=0.011 n=18 n=18 MST (days) 1 year survival 2 year survival Vaccinated group % 67% Historical control group % 28% Commercialization anticipated this year via licensee, Aratana Therapeutics Mason N, et al. Clin Cancer Res [epub ahead of print] pii:clincancerres

26 ADXS-HER2: Phase 1B Dose-Escalation Study in HER2 Expressing Solid Tumors PRIMARY ENDPOINT: SAFETY AND RP2 DOSE PD, disease progression; RP2, Recommended phase 2 Dose level 1 commenced with no DLTs to date 26

27 Axalimogene Filolisbac: Open Label Phase 2 Study in HPV+ Oropharyngeal Squamous Cell Carcinoma (HPVOPC) ADXS-HPV Prior to Robot-Assisted Resection (TORS) of HPVOPC (N=22) Window of Opportunity Trial Study Arm N = 22 ADXS Pre-surgery Biopsy 1 Treatment HPV test ADXS ADXS PBMCs PBMCs PBMCs TORS (Biopsy 2) PBMCs Observe N = 10 No Treatment HPV test PBMCs PBMCs PBMCs PBMCs Mt Sinai Medical Center Study Arm: ADXS (Axalimogene Filolisbac) Alone Primary stage 2 4 oropharyngeal squamous cell carcinoma 2 doses of CFU as an 80-mL infusion over 15 minutes HPV+ Observational Arm: No Treatment Controls Routine surgical preparation Krupar R, et al. Presented at AACR LB-095.

28 Late Breaking AACR Data: Proof of Mechanism Validates Lm Technology as an I-O Approach Window of Opportunity Study: Summary of AACR Abstract Increase in CD8+ T-Cells and Decrease in PD-L1 AXAL-induced changes in T-cell infiltration and checkpoint expression in tumor microenvironment Study Design Newly diagnosed HPV+ squamous cell carcinoma of the oropharynx 8 treated and 3 control patients Results Detection of E6 and/or E7 specific T-cell response in peripheral blood in 5 of 8 treated patients Potential AXAL-induced changes in the tumor microenvironment with regard to T-cell infiltration and immune checkpoint molecule expression Decrease in tumor infiltrating FOXP3 + Tregs observed in 3 out of 8 treated patients Decrease of serum cytokines involved in T cell activation suggest increased consumption FI-Bkgd Increase in Lymphocyte Infiltration preadxs postadxs Tumor-host interface Tumor-host interface IL-15 FI-Bkgd Decrease in Serum Cytokines IL-9 FI-Bkgd TNFa TNFα Krupar R, et al. Presented at AACR LB-095. p= V2 V4 V5 preadxs postadxs posttors Timepoints p= p= V2 V4 V5 preadxs postadxs Timepoints posttors V2 preadxs V4 postadxs Timepoints V5 posttors 28

29 On-Site Manufacturing Fully integrated in-house development, manufacturing, and testing to be constructed in 2016 Process development suite Solution preparation Inoculum preparation Bulk drug substance manufacturing Bulk drug product manufacturing Packaging NEO manufacturing QC labs Warehouse storage & distribution Increased manufacturing capability and capacity will allow Advaxis to manufacture its own material and reduce reliance on CMOs, improving supply flexibility, scalability, lead times, and costs of goods 29

30 Financial Summary & Leadership Accountability Cash on hand as of April 30, 2016 Capital raised since October '13 Cash Summary No Debt $94.6M ~$165M Basic Shares Outstanding Warrants and Options Equity Summary 34.0M Fully Diluted 40.5M 3.1M and 3.4M Out of Pocket Funds (1) Company Incentive Awards (1) Gross $ net shares vested unvested Daniel J. O'Connor $741, , ,030 33,333 Gregory T. Mayes $200,435 28,805 55,114 37,500 Robert G. Petit $148,767 30,129 62,831 28,879 Sara M. Bonstein $144,205 27,998 52,827 - Management voluntarily purchases restricted stock directly from the Company every two weeks at market price 1) Above figures are as of June 2, Represents RSU awards & share purchases only. Does not include options and/or warrants. 30

31 Anticipated Milestones Programs Event Timing Finish SPA process & initiate enrollment of randomized Phase 3 monotherapy study in high-risk, locallyadvanced cervical cancer (AIM2CERV) Mid 2016 Complete enrollment of Stage 2 of Phase 2 monotherapy study in metastatic cervical cancer (GOG 0265) Late 2016 Complete enrollment of Phase 1 study in combination with MedImmune s durvalumab for the treatment of HPV-associated head and neck cancer and metastatic cervical cancer 1H 2016 Axalimogene Filolisbac Commence and complete enrollment of Phase 2 study in combination with MedImmune s durvalumab 2H 2016 Commence enrollment for Phase 2 study in HPV positive, non-squamous, non-small cell lung cancer following first-line induction chemotherapy 1H 2016 Complete enrollment of high dose expansion cohort in Phase 2 study in recurrent cervical cancer 1H 2016 Initiate Phase 2 study in metastatic anal cancer (FAWCETT) 1H 2016 Present data from Phase 1/2 window of opportunity study in HPV positive head and neck cancer 1H 2016 ADXS-HER2 Complete enrollment and establish safe dosing level in preparation for expansion in Phase 1b monotherapy study in solid tumors expressing HER2 1H 2016 ADXS-PSA Complete enrollment of Part A Phase 1/2 combination study with KEYTRUDA in prostate cancer 1H 2016 Commence and complete enrollment of Part B Phase 1/2 combination arm with KEYTRUDA 2H 2016 ADXS-NEO Progress toward filing an IND; conduct preclinical studies in collaboration with academic institutions, including Memorial Sloan Kettering Cancer Center (MINE ) 2016 ADXS-TNBC Finalize preclinical work for multiple-antigen construct with goal of filing an IND in

32 Our Lm Technology utilizes the efficiency of the entire immune system by teaching it to recognize the tumor as a threat, and by weakening the tumor s defenses. Once educated by Lm Technology, the immune system specifically, its killer T cells are enabled to do their job and work to destroy the cancer. 305 College Road East Princeton, NJ ir@advaxis.com