RBC Capital Markets Healthcare Conference February 23, 2016
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 http://www.sec.gov. 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
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 ~50 employees with lab, office, manufacturing facilities, and vivarium located in Princeton, NJ Financial Snapshot Raised ~$165M since October 2013 Cash: ~$112M as of October 2015 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
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
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 5
The Intelligent Immune Response Lm Technology stimulates a tumor-targeted immune response...so that cancer can be recognized...and killed Attenuated Lm trigger a robust immune response and bioengineered plasmids generate a fusion protein, tllo-taa TAA activates cytotoxic T-cells targeted against the tumor T-cells target TAA on tumor cells and tllo causes inhibition of Treg and MDSC function in the TME, reducing the tumor s protective shield APC, antigen presenting cell; Lm, Listeria monocytogenes; MHC, major histocompatibility complex; TCR, T-cell receptor; MDSC, myeloid-derived suppressor cells; TAA, tumor-associated antigen; tllo, truncated listeriolysin O; Treg, regulatory T cell; TME, tumor microenvironment 6
Active or Planned Clinical Trials Axalimogene filolisbac, ADXS-PSA, and ADXS-HER2 PRODUCT INDICATION PHASE 1 PHASE 2 PHASE 3 Partner CERVICAL CANCER* AIM2CERV Adjuvant Randomized vs Placebo Phase 3 M Metastatic GOG 0265 Phase 2 Metastatic Single Arm High Dose Phase 1/2 Axalimogene filolisbac C Metastatic Combo with durvalumab Phase 1/2 HEAD AND NECK CANCER* M Neoadjuvant Window of Opportunity - Mount Sinai Phase 2 ANAL CANCER* RTOG Adjuvant Randomized vs Control Phase 2/3 M Adjuvant Single Arm High Risk Brown University (BrUOG) Phase 1/2 Metastatic (FAWCETT) Phase 2 ADXS-PSA PROSTATE CANCER C Metastatic Combo with KEYTRUDA (pembrolizumab) Phase 1/2 HER2-POSITIVE SOLID TUMORS (INCLUDING OSTEOSARCOMA*) ADXS-HER2 M Metastatic Single Arm Phase 1 Osteosarcoma Phase 2 * Orphan Drug Designation C Combination M Monotherapy Active Planned All trademarks and logos are the property of their respective owners. 7
Axalimogene Filolisbac: Open Label 2-Stage Phase 2 Study In Recurrent Cervical Cancer (GOG 0265) PRIMARY EFFICACY ENDPOINT: 12-MONTH SURVIVAL AXAL Monotherapy 1x10 9 colony forming units (cfu) x 3 doses q 28 days (month 1, 2, 3) as an 80 ml infusion over 15 min N = ~67 (Stage 1 and 2) Persistent or recurrent metastatic cervical cancer (PRmCC) 1 prior chemotherapy regimen for PRmCC, excluding that received as a component of primary treatment GOG PS 0/1 Measurable disease 1 target lesion (RECIST 1.1) Axalimogene filolisbac Day 0 MONTH 1 MONTH 2 MONTH 3 Axalimogene filolisbac Day 28 Axalimogene filolisbac Day 56 Tewari KS, Monk BJ. CurrOncolRep. 2005; 7(6):419-34; GOG, Gynecologic Oncology Group https://www.clinicaltrials.gov/ct2/show/nct01266460 8
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) 2015 3 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):1069-74. Presented by Thomas Herzog, MD, at AGOS 2015 9
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 2015 10
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 of Stage 1 GOG 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% 38.5% of patients (n=10) treated with AXAL achieved12-month survival, exceeding historical rates in this difficult to treat population Avastin met the predefined criteria to progress to the second stage of enrollment (median OS = 7.3 mo and 12-mo OS = 30%) GOG 0265 included a more heavily pretreated population than previous trials and included post-progression CT and Avastin patients 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 0-1 1 1-2 1-3 1998 2015 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 11
107008 100008 121006 116003 110016 109004 109009 105007 128001 107003 101007 110012 110017 104003 124011 116007 111005 104006 121001 107006 103009 128002 107007 110010 104008 107005 113001 111001 115004 103013 112005 126001 113010 110008 104001 100019 104005 107009 111006 115008 116006 100004 110004 110003 121007 100011 105009 107002 101006 100015 103015 121002 101008 103011 118001 111002 110007 103003 100012 101001 103017 103008 103012 110002 103010 103014 110009 115005 119005 Change from Baseline (%) Axalimogene Filolisbac: Randomized Phase 2 Study Tumor Response Data 440 420 400 380 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 60 40 20 0-20 -40-60 -80-100 PD Axalimogene filolisbac showed activity against recurrent cervical cancer with and without standard chemotherapy 3 doses of axalimogene filolisbac as monotherapy produced CRs in a difficult to treat patient population with few treatment options PD PD SD SD N=66 response-evaluable patients ADXS CR CR SD SD SD SDSDSD SD SD SD PR PR CR ADXS/CIS LTS Long Term Survivor PD Partial Disease SD Stable Disease PR Partial Response CR Complete Response LTS = alive > 18 months from randomization CR 12
Axalimogene Filolisbac: Next Steps Phase 3 AIM2CERV Study Schema RANDOMIZATION 1:2 BETWEEN REFERENCE AND TREATMENT GROUPS Patient characteristics: High risk, locally advanced cervical cancer Cisplatin (at least 4 wks exposure) and Radiation (minimum 40 Gy external beam radiation therapy) FIGO stage I-II with positive pelvic nodes FIGO stage III-IV Any FIGO stage with para-aortic nodes Reference Group Placebo IV Up to 1 yr RANDOMIZE Treatment Group AXAL (1 x 10 9 cfu) Up to 1 yr Primary Endpoint: Progression Free Survival 13
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 https://www.clinicaltrials.gov/ct2/show/nct01671488 14
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 0.5 33 months N = 10 treatment patients Patient progressed systemically Patient expired unrelated to study treatment 0 200 400 600 800 1000 1200 Relapse Free Survival (Days)* Note: Patient #1 enrolled but was never treated on study On ADXS11-001 RFS Hx 3-yr RFS in stage-matched population ~45% Perez K et al. IANS 2015; Abstract 23. 15
Axalimogene Filolisbac + PD-L1/PD-1 Initial Phase 2/3 Study in Anal Cancer: FAWCETT Persistent/recurrent, loco-regional or metastatic anal cancer or HPV+ squamous cell carcinoma of the rectum that are either treatment naïve in the metastatic setting or have progressed/become intolerant to platinum therapy Axalimogene filolisbac monotherapy in Stage 1 at 1x10 10 cfu in a 3+3 dose escalation design with interim analysis Axalimogene filolisbac + PD-L1 or PD-1 inhibitor in Stage 2 vs. SOC arm Stage 1 Axalimogene filolisbac Dose level: Dose escalation to 1x10 10 cfu d1 wk 1,4,7,9 (1 cycle) Cycles 2+ up to 2 years N = 20 RR>10% or 6-month PFS>25% Stage 2 Axalimogene filolisbac + PD-L1/PD-1 Dose level: 1x10 10 cfu d1 wk 1,4,7,9 (1 cycle) PD-L1/PD-1 d1 q 2wks N = 40 AXAL PD-L1/PD-1 SOC Arm Cisplatin + 5-FU +/- radiation Cisplatin 100 mg/m2 IV day 2 Continuous infusion 5-FU 1000 mg/m2/d IV days 1-5 (q 4 weeks) N = 40 Proceed to Stage 2 if response rate >10% by either RECIST 1.1 or irrecist, or if 6-month progression free survival (PFS) rate >25% Primary endpoints: Overall response rate, 6-month PFS, and safety & tolerability Secondary endpoints: Duration of response, PFS, and overall survival WEEK 1 WEEK 4 WEEK 7 WEEK 9 AXAL AXAL AXAL WEEK 1 WEEK 4 WEEK 7 WEEK 9 PD-L1/PD-1 PD-L1/PD-1 PD-L1/PD-1 REPEAT Q 12 WEEK CYCLES Up to PD or 2 years REPEAT Q 12 WEEK CYCLES Up to PD or 2 years Interim Analysis AXAL AXAL AXAL AXAL Final Analysis 16
Percent Survival Preclinical Rationale for Checkpoint Combination Trials AXAL + PD-1 HPV Tumor Model TC-1 tumor implantation Tx 1 Tx 2 0 8 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 published in Journal for ImmunoTherapy of Cancer 2013, 1:15 doi:10.1186/2051-1426-1-15 17
Combination with anti-pd-l1 (durvalumab) Metastatic Cervical Cancer or Head & Neck Cancer HPV+ SCCHN or metastatic cervical cancer patients with measurable disease and ECOG status 0-1 Phase 1: dose confirmation safety run-in with 6 to 12 patients receiving combination of AXAL fixed dose + durvalumab 3+3 safety design; progress to expansion with 20 patients (HNSCC) Phase 2: Randomize 90 recurrent/metastatic cervical cancer patients 1:1 onto durvalumab monotherapy or combination with AXAL Following the completion of enrollment and the safety evaluation of Cohort 1 in Phase 1 in 2015, the study will complete enrollment of the expansion cohort in the first half of 2016 Phase 2 of the study will commence once dose determination is made, with enrollment completed in 2016 Phase 1 AXAL + durvalumab AXAL d1 wk 1,4,7 q12 wks + durvalumab d1 q 3wks N = 6 to 12 with expansion to 20 WEEK 1 WEEK 4 WEEK 7 REPEAT Q 12 WEEK CYCLES durvalumab durvalumab durvalumab AXAL AXAL AXAL Up to PD or 1 year with 4 years surveillance Phase 2 (1:1 Randomization) Durvalumab Monotherapy (N = 45) durvalumab d1 q 2wks WEEK 1 WEEK 4 WEEK 7 REPEAT Q 12 WEEK CYCLES Up to PD or 1 year with 4 years Up to surveillance PD or 1 year durvalumab durvalumab durvalumab AXAL + durvalumab (N = 45) AXAL d1 wk 1,4,7 q12 wks + durvalumab RP2D N = 90 Total durvalumab durvalumab durvalumab AXAL AXAL AXAL Up to PD or 1 year with 4 years surveillance https://www.clinicaltrials.gov/ct2/show/nct02291055 18
ADXS-PSA: Phase 1/2 Dose Escalation and Safety Study Alone and Combined with PD-1 (Keytruda ) N = 21 (Part A); N = 30 (Part B) [Total N = 51] Pretreated metastatic castration-resistant prostate cancer (CRPC) No more than 3 prior systemic treatment regimens with chemotherapy, hormonal, or immunotherapy or more than 1 prior chemotherapeutic regimen in the metastatic setting Part A ADXS-PSA Monotherapy mtpi Design (Part A) to determine recommended Phase 2 dose Following the completion of enrollment and the safety evaluation of ADXS-PSA in Part A, Part B combination arm with Keytruda will commence in the first half of 2016. Part B ADXS-PSA Dose = Part A recommended Phase 2 dose (DL-1) + Keytruda WEEK 1 WEEK 4 WEEK 7 REPEAT Q 12 WEEK CYCLES Dose level 1: 1x10 9 cfu d1 wk 1,4,7 q12 wks Dose level 2: 5x10 9 cfu d1 wk 1,4,7 q12 wks Dose level 3: 1x10 10 cfu d1 wk 1,4,7 q12 wks Up to PD or 2 years N = 21 ADXS-PSA ADXS-PSA ADXS-PSA Part B WEEK 1 WEEK 4 WEEK 7 REPEAT Q 12 WEEK CYCLES ADXS-PSA + Keytruda ADXS-PSA Part A Dose DL1 d1 wk 1,4,7 q12 wks ADXS-PSA ADXS-PSA ADXS-PSA Keytruda 200 mg d1 q 3wks in 12 wk cycles N = 30 Up to PD or 2 years Keytruda Keytruda Keytruda https://clinicaltrials.gov/ct2/show/nct02325557 19
Checkpoint Inhibitor Market Immuno-oncology products are expected to generate ~$9 billion across the world by 2022 2 The cancer therapeutic vaccines segment of the market is expected to have sales of $1.2 billion 2 Current immunotherapy products, such as the checkpoint inhibitors, work by shutting down a tumor s ability to disrupt the immune system and thereby allowing dormant T cells to become active and attack the tumor Rather than set up an indirect attack on cancer, Advaxis products directly activate the immune system to kill tumor cells As a platform for immune activation, Advaxis Lm Technology is positioned to become the universal donor of immuno-oncology, with broad applicability as a combination therapy across tumor types 1 Webster RM. The immune checkpoint inhibitors: where are we now? Nature Reviews Drug Discovery 2014; 13: 883-884. 2 Insight Pharma Reports. Cancer Immunotherapy: immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapies. Published 9/30/2014. 20
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) 2 1 5 2 10 Fatigue 1 1 7 2 11 GI Disorders Vomiting 2 1 8 1 12 Nausea 2 1 9 2 14 Cardiovascular Arrhythmias 0 1 1 1 3 Tachycardia 0 0 1 1 2 Hypotension 0 0 0 0 0 Hematological parameters Thrombocytopenia 0 0 5 0 5 Biochemical parameters (increase) γ-gt 0 2 0 0 2 Alkaline Phosphatase 1 1 4 1 7 ALT 1 1 1 0 3 AST 1 1 5 1 8 BUN 0 0 0 0 0 CREA 0 0 0 0 0 Cardiac Troponin I 0 0 1 0 1 ADXS-HER2 and Overall Survival p=0.011 n=18 n=18 MST (days) 1 year survival 2 year survival Vaccinated group 956 78% 67% Historical control group 423 55% 28% Commercialization anticipated this year via licensee, Aratana Therapeutics 26 21
ADXS-HER2: Phase 1B Dose-Escalation Study in HER2 Expressing Solid Tumors PRIMARY ENDPOINT: SAFETY AND RP2 DOSE ADXS-HER2 Monotherapy Dose level 1: 1x10 9 cfu q 3 wks Dose level 2: 5x10 9 cfu q 3 wks Dose level 3: 1x10 10 cfu q 3 wks N < 18 (Dose finding); N < 80 (Expansion phase) [Total N ~100] 3 WEEKS 3 WEEKS 3 WEEKS UP TO PD OR 2 YEARS HER2-positive solid tumor (>1+ positivity in 1% of cells by IHC) Disease progressed or intolerant to standard therapy ADXS-HER2 Day 0 ADXS-HER2 Day 21 ADXS-HER2 Day 42 If no DLT, next Dose level initiates ECOG PS 0-1 3+3 Phase I Design Dose level 1 commenced with no DLTs to date PD, disease progression; RP2, Recommended phase 2 https://clinicaltrials.gov/ct2/show/nct02386501 22
HIGHLY PERSONALIZED NEOEPITOPE-BASED CANCER IMMUNOTHERAPY
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 24
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 80-100 plasmid copies per bacteria Payload for 25-50 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 25
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 26
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 27
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 28
Financial Summary & Leadership Accountability Cash on hand as of October 31st Capital raised since October '13 Cash Summary No Debt $112.2M ~$165M Basic Shares Outstanding Warrants and Options Equity Summary 33.6M Fully Diluted 38.8M 3.2M and 2.0M Out of Pocket Funds (1) Company Incentive Awards (1) Gross $ net shares vested unvested Daniel J. O'Connor $694,923 155,394 124,076 66,667 Gregory T. Mayes $189,564 27,676 55,114 37,500 Robert G. Petit $137,475 29,078 50,931 49,986 Sara M. Bonstein $104,109 26,953 34,530 33,333 Management voluntarily purchases restricted stock directly from the Company every two weeks at market price 1) Above figures are as of January 4, 2016. Represents RSU awards & share purchases only. Does not include options and/or warrants. 29
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 2016 2016 30
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 www.advaxis.com ir@advaxis.com