CORPORATE PRESENTATION March 2017
Forward-Looking Statements 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 SEC filings including, but not limited to, its report on Form 10-K for the fiscal year ended October 31, 2016, which is available at http://www.sec.gov. Any forward-looking statements set forth in this presentation speak only as of the date of this presentation. We do not intend to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof other than as required by law. 2
Targeted Immunotherapies Bacterial Vector System Bioengineered Listeria monocytogenes (Lm) generates T-cell response capable of targeting multiple tumors Stimulates innate and adaptive immune response to attack cancer cells Single-agent activity demonstrated; potential for combination synergies Manageable safety profile Versatile platform Highly proprietary technology, straight-forward manufacturing Broad Pipeline Lead candidate axalimogene filolisbac in Phase 3 in cervical cancer; Phase 2 in anal and head & neck cancers 2 other clinical assets targeting prostate cancer and HER-2 positive solid tumors ADXS-NEO IND accepted in March 2017 - in development collaboration with Amgen ADXS-HOT IND planned for 2017 Addressing High Unmet Need in Cervical Cancer 12-month survival rates in metastatic cervical cancer exceed historical GOG studies Phase 3 AIM2CERV trial under way in patients with high-risk, locally advanced cervical cancer Phase 3 in metastatic cervical cancer to begin in 2017 EMA filing in metastatic cervical cancer in 2017 Fast-Track Designation, Orphan Drug Designation 3
Experienced Management Team Daniel O Connor Chief Executive Officer Robert Petit Chief Scientific Officer Sara Bonstein Chief Financial Officer Chris Duke Chief Operating Officer Mayo Pujols Sr. Vice President, Technical Operations Thomas Hare Sr. Vice President, Product Development Robert Ashworth Sr. Vice President, Regulatory, Quality & Compliance Ranya Dajani Vice President, Corporate Development 4
The Bacterial Vector System Provides a Unique Multi-pronged Approach to Immunotherapy Trigger & Target Response/Recognize Cancer Activate Against Target T-cell Direct Tumor Effect Disarm & Attack TME Defense Mechanisms Bacterial vector (attenuated listeria monocytogenes or Lm) system triggers robust innate and adaptive immune response Embedded bioengineered plasmids generate fusion protein truncated listeriolysin O tumor associated antigen (tllo-taa), Cancer is recognized tllo-taa activates cytotoxic T cells T cells targets tumor antigen of choice Reduces the tumor s protective shield tllo-taa inhibits Tregs and myeloid-derived suppressor cell (MDSC) in tumor microenvironment Enables destruction 5
Broad Clinical Pipeline Targeting Multiple Tumor Types Product Candidate Target Population IND Ph 1 Ph 2 Ph 3 High risk locally advanced cervical cancer AXALIMOGENE FILOLISBAC Metastatic cervical cancer Metastatic cervical and head & neck cancer Combination with durvalumab Metastatic anal cancer ADXS-PSA ADXS-HER2 Metastatic prostate cancer Combination with KEYTRUDA (pembrolizumab) HER2-positive metastatic solid tumors Pediatric osteosarcoma ADXS-NEO Multiple cancers by targeting neoantigens ADXS-HOT Multiple cancers by targeting hotspot mutations On-going Planned 6
ADXS-NEO: Ideal Platform for Personalized Immunotherapies Personalized cancer immunotherapies have evolved Letting patient s unique cancer mutations tell us how to target the tumor ADXS-NEO, a preclinical asset, has demonstrated tumor control in an in vivo model Ideal platform for activating the immune system against cancer neoantigen: Directly activates APC through an attenuated but specific infection Delivers a large payload of neoantigen for producing a T cell response Decreases the number of Tregs and MDSCs in the tumor microenvironment Has been shown to be synergistic with checkpoint inhibitors in preclinical studies Manufacturing process meets requirement for scalability, reasonable turnaround and cost 7
Moving Away from One Size Fits All Cancer Treatment Efficient Process for Highly Personalized Immunotherapy for Multiple Cancers Tumor biopsy, parallel sequencing identify unique neoantigen specific to an individual patient s tumor Sequencing data used to bioengineer ADXS- NEO construct Tumor biopsy to treatment infusion is approximately 8 weeks Global Collaboration $40M upfront $25M stock purchase $475M in achievement-based milestones Amgen fully funding all development and commercial activities Tiered royalties on net sales IND accepted March 2017 8
Axalimogene Filolisbac: Lead Candidate Targeting High Unmet Medical Need in HPV-associated Cancers Targets HPV-associated Cancers Promising Clinical Data Manageable Safety Profile Clinical Studies: Cervical Cancer Adjuvant Phase 3 - Underway Metastatic Phase 3 Planned Anal Cancer Phase 2 - Underway Head & Neck Cancers Phase 2 Combo - Underway Cervical Cancer: 12-month OS rates for axalimogene filolisbac exceeded historical GOG studies in metastatic setting Combination therapy w/ durvalumab in Recurrent/Metastatic Granted FDA SPA, Fast- Track and Orphan status Granted ATMP by EMA CAT; EMA filing planned 2017 Clinical Profile Includes: Consistent safety profile in preliminary findings GOG-0265 Clinical Study demonstrates axalimogene filolisbac well tolerated, manageable adverse events HPV - Human papillomavirus; AXAL - Axalimogene Filolisbac; FDA - Food and Drug Administration; SPA - Special Protocol Assessment; ATMP - Advanced Therapy Medicinal Product; EMA - European Medicines Agency; CAT - Committee for Advanced Therapies 9
High Unmet Medical Need in Cervical Cancer An estimated 12,990 U.S. CASES of invasive cervical cancer are expected to be diagnosed in 2016 1 High Risk Locally Advanced Cervical Cancer Total U.S. Treatment Eligible Patients 2 ~4,900 Recurrent/Metastatic Cervical Cancer Total U.S. Treatment Eligible Patients 2 ~5,000 4,120 DEATHS Estimated in U.S. from cervical cancer are expected in 2016 1 Limited Treatment Options: Surgery and/or chemoradiation Very few therapies under development Only 1 approved product in the last 30 years, bevacizumab approved in 2014 AIM2CERV only Phase 3 Study currently underway Globally there are 500,000 patients diagnosed with cervical cancer 3* IIIA IIIB IVA IVB ~16% 1~5% ~35% ~32% Poor 5-year survival rate in late stage cervical cancer 3 0% 25% 50% 75% 100% 1. National Cancer Institute. 2. Surveillance, Epidemiology, and End Results Program. SEER stat fact sheets: cervix uteri cancer. http://seer.cancer.gov/statfacts/html/cervix.html. Accessed November 7, 2016; 3. American Cancer Society/ National Cancer Institute 4. Monk BJ, et al. J Clin Oncol. 2009;27:4649-4655; *Estimates are for 2008 and reflect persons with detectable infection with any of 37 different HPV types, not just types 6, 11, 16, 18, 31, 33, 45, 52, and 58. 10
Phase 2 GOG 0265: Study of Axalimogene Filolisbac (AXAL) in 50 Patients with Persistent or Recurrent Metastatic Cervical Cancer Persistent or recurrent squamous or nonsquamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix Stage 1 N=26 axalimogene filolisbac q28d X 3 Safety, tolerability and efficacy hurdle met for initiation of Stage 2 Two-stage Trial Design Stage 2 N=37 axalimogene filolisbac q28d Until PD, unacceptable toxicity, or consent withdrawn Endpoints Primary: 12-month OS, tolerability/safety Secondary: PFS OS ORR Study sponsored by Advaxis and Cancer Therapy Evaluation Program and coordinated by the Gynecologic Oncology Group (GOG) in collaboration with the National Cancer Institute. https://www.clinicaltrials.gov/ct2/show/nct01266460. Endpoints: ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival. Tewari KS, et al. Curr Oncol Rep. 2005;7:419-434. On October 24, 2016, Advaxis announced early closure of stage 2 which is no longer enrolling. 11
AXAL - GOG Study 0265: 12-month Overall Survival of 38% Achieved 12-month survival of 38% (n=19/50; Primary Endpoint) Number of Patients: 50 Events: 43 (86%) Censored: 7 (14%) Median OS: 6.2 months 95% CI: (4.4 12.3) Model-based historical control predicted 25% 12-month survival* 38% survival observed represents a 52% improvement over predicted survival Safety profile consistent with previous findings: Most common TRAEs (>30%) were Grade 1 2 fatigue, chills, anemia, nausea Pursuing filing for approval in EU and launching Phase 3 trial in metastatic cervical cancer TRAEs: treatment related adverse events *Calculated model-based historical control determined from data in 17 previous GOG cervical cancer studies comprised of ~500 patients with similar prognostic factors 12
34 patients 44 patients 29 patients 40 patients 24 patients 25 patients 44 patients 32 patients 32 patients 23 patients 32 patients 27 patients 23 patients 25 patients 25 patients 25 patients 46 patients 50 patients Study GOG-0265: AXAL Outperforms All Historical GOG Studies in Metastatic Cervical Cancer With 38% 12-Month Overall Survival 40% 12-Month Overall Survival Axalimogene filolisbac 35% 30% These (0265) data demonstrate a meaningful 25% 20% 15% improvement in 12-month OS rate compared to historical GOG studies. 10% 5% 0% Warner K. Huh, MD Director, Division of Gynecologic Oncology at the University of Alabama, Birmingham, and lead investigator of study GOG-0265 13
Study GOG-0265: 66-Year-old Patient Treated with Axalimogene Filolisbac, Complete Response Ongoing Diagnosis: squamous cell cancer of the cervix Pelvic recurrence 2006 2007 2014 July 2015 Aug. Sept. Radical hysterectomy Treated with: paclitaxel/carboplatin bevacizumab pelvic radiation Systemic recurrence June 2015 Enrolled in GOG-0265 Dose 1 Dose 2 Dose 3 Axalimogene Filolisbac May 2016 Complete response Treatment-related AEs: Grade 1-2 fatigue, chills, fever, nausea and Grade 3 hypotension, cytokine release syndrome; No Grade 4-5 TRAEs reported Results may not be typical; further study is warranted. 14
Immunotherapy Checkpoints: Pembrolizumab Monotherapy in HPV+ Cervical Cancer Data from the second-line and later cervical cancer cohort of KEYNOTE-028 Phase 1b study were presented at ASCO 2016 (n = 24) Preselected population: PD-L1+ patients only No CRs; PRs in 4 (17%) patients; SD in 3 (13%) patients Median PFS, 2 months; median OS, 9 months Analysis of Pembrolizumab in Relapsed/Refractory (R/R) Cervical Cancer Patients, n (%) PFS OS 6-month survival 21% 67% 12-month survival 8% 33% AEs were consistent with the established profile for pembrolizumab AE, adverse event; CR, complete response; PD-L1, programmed cell death protein 1 ligand 1; PR, partial response; SD, stable disease. Presented by Jean-Sebastien Frenel at 2016 ASCO Annual Meeting. 15
Axalimogene Filolisbac Demonstrates Manageable Safety Profile Adverse Event Summary (n = 26) AE Grade 1 2 Grade 3 Grade 4 Patients with 1 TRAE, n (%) 24 (92) 4 (15) 1 (4)* TRAEs occurring in 10% of patients Fatigue 15 (58) - - Chills 14 (54) - - Fever 11 (42) - - Nausea 10 (39) - - Headache 9 (35) - - Hypotension 7 (27) 2 (8) - Vomiting 6 (23) - - Cytokine release syndrome 5 (19) 3 (12) - Myalgia 5 (19) - - Abdominal pain 4 (15) - - General pain 4 (15) - - Flu-like symptoms 3 (11) - - AST elevation 3 (11) - - *The observed grade 4 TRAE recorded in 1 patient (lung infection and sepsis) was considered possibly related to treatment. AST, aspartate aminotransferase. Huh W, et al. ASCO 2016. Abstract 5516. 16
Phase 3 AIM2CERV Studies Axalimogene Filolisbac as Adjuvant Monotherapy to Prevent Recurrence in High-Risk Cervical Cancer HRLACC FIGO stage I II with positive pelvic nodes FIGO stage III IVA Any FIGO stage with para-aortic nodes Treatment with cisplatin (at least 4-wks exposure) and radiation (minimum 40-Gy external beam radiation therapy) Randomize Placebo IV Up to 1 year N=150 Axalimogene Filolisbac (1 X 10 9 CFU) Up to 1 year N=300 Primary Endpoint: DFS Baseline tumor imaging must be performed within 28 days prior to the first study treatment infusion AIM2CERV Axalimogene Filolisbac Immunotherapy Following Chemo/Radiation in Patients who have High Risk Locally Advanced Cervical Cancer (HRLACC) CFU, colony-forming unit; DFS, disease-free survival; FIGO, International Federation of Gynecology and Obstetrics; HRLACC, high-risk locally advanced cervical cancer; IV, intravenous. 1. Herzog T, et al. SITC 2016. Poster 145. 17
AIM2CERV by the Numbers 450 Patients ~20 Countries ~150 Global sites July 2016 Q3 2016 Q1 2017 1H 2018 4Q 2018 2H 2020 FDA Special Protocol Assessment Initiate Study Start-up First patient enrolled Ex-US sites to open 50% patient enrollment Last patient enrolled Study completed Event-driven study: 184 events (recurrence or death due to any cause) required prior to efficacy analysis Estimated timeline Timeline is based on current estimates. FDA, US Food and Drug Administration. 18
Phase 2 Study Underway with Axalimogene Filolisbac In Combination with Durvalumab to Treat Cervical and Head and Neck Cancers Part 1: Dose Escalation, Dose Determination Part 2: N=90 Cervical Cancer Only Axalimogene Filolisbac + durvalumab combination Part 2 N=11 enrolled/treated to date Axalimogene Filolisbac: 1x10 9 (fixed) durvalumab: 3+3 dose-confirmation Dose Level 1: 3 mg/kg, N=5 cervical cancer Dose Level 2: 10 mg/kg, N=3; cervical cancer; N=3; HPV+ SCCHN Part 1 Objectives Safety Tolerability RP2D Randomize Durvalumab monotherapy 10mg/kg Axalimogene Filolisbac + durvalumab 1x10 9 + RP2D Objectives: PFS Overall safety Tumor response Expansion Phase N= 20 Axalimogene Filolisbac + durvalumab (RP2D) in SCCHN only In collaboration with: HPV, human papillomavirus; RP2D, randomized phase 2 dose; SCCHN, squamous cell cancer of head and neck. 19
Axalimogene Filolisbac + Durvalumab: Encouraging preliminary activity with 1 CR to date Patient Disposition, Treatment Received, and Response Assessment Preliminary Safety Findings TRAEs included chills and/or rigor, nausea, hypotension, diarrhea, fatigue, tachycardia & headache 2 patients experienced grade 3 chills and/or rigors; 1 patient experienced grade 3 diarrhea; 1 patient experienced grade 4 hypotension. Preliminary data indicate encouraging antitumor activity of the combination immunotherapy regimen *In 3 patients (Patients 3, 7, and 10) no response assessment was made because a post-baseline scan was not obtained prior to elective study withdrawal. 20
Axalimogene Filolisbac + Durvalumab: 49-Year-old Patient Achieves Complete Response at Dose Level 1 Diagnosis: 49 y/o woman -squamous cell carcinoma of the cervix September 2015 Axalimogene Filolisbac - 1 10 9 CFU + durvalumab - 3 mg/kg May 2016 2011 2013 2015 Sep 15 May 16 Treated three rounds of systemic chemotherapy Axalimogene Filolisbac 1 10 9 CFU durvalumab 3 mg/kg September 2015 Enrolled study with metastatic cervical cancer refractory to treatments Oct 2015 Nov 2015 Dec 2015 Jan 2016 Feb 2016 Mar 2016 April 2016 May 2016 June 2016 Jul 2016 Aug 2016 Clinical Hold Jan 2016 Partial Response May 2016 PET/CT Scan Complete Response Preliminary Safety Grade 1 transient chills, fatigue, fever, nausea, vomiting, headache, hypotension Grade 2 rigors Results may not be typical; further study is warranted. 21
Significant Need for Therapies to Treat Metastatic Anal Cancer and Prevent Recurrence An estimated 7,500 U.S. CASES of anal cancer expected to be diagnosed in 2016 Recurrent/Metastatic Anal Cancer Total U.S. Treatment Eligible Patients ~2,400 High Risk Locally Advanced Anal Cancer Total U.S. Treatment Eligible Patients ~4,100 1,080 DEATHS Estimated U.S. deaths from anal cancer are expected in 2016 Limited Options: No FDA approved anal cancer chemotherapy Limited therapies under development Anal Cancer Cases Caused by HPV 92% In the US there were 7,200 IIIB patients diagnosed with anal cancer in 2011 IIIA 48% IV 21% 43% Poor 5-year survival rate under 50% in late stage anal cancer* 0% 25% 50% 75% 100% *American Cancer Society 22
Phase 1/2 BrUOG Study in High Risk Advanced Anal Cancer with Axalimogene Filolisbac + Mitomycin, 5-FU and Radiation Axalimogene Filolisbac 1 10 9 cfu 4 (1 prior to chemort and 3 after, q28 days) as a 500-mL infusion over 30 min N = 25 Primary Stage 2 3 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 + chemo Axalimogene filolisbac #2 Day +10 post-imrt Axalimogene filolisbac #3 BIOPSY Followup Axalimogene filolisbac #4 Primary efficacy endpoint is 6-month CR rate 11 patients enrolled; continuing to track 9 patients who completed treatment and achieved complete responses No further enrollment given Phase 3 study plans https://www.clinicaltrials.gov/ct2/show/nct01671488 *BrUOG, Brown University Oncology Group. Perez K, et al. IANS 2015. Abstract 23. 23
Axalimogene Filolisbac: Phase 1/2 Study in Anal Cancer Preliminary Results Show Early Response, Lack of Recurrence and Axalimogene Filolisbac Signal Relapse Free Survival Data Adverse Event Flu-like symptoms Grade 2 1 Migraine 1 Hypotension 1 Grade 3 Hypokalemia* 1 Chills/rigors 3 2 Nausea 2 Back Pain 1 1 Fever 2 There were no Grade 4 adverse events. Summary All patients who have completed RT and received treatment achieved a CR at six months (N = 9) No evidence of recurrence Historical 3-year recurrence rate in similar patient population = ~45% Follow-up duration: 0.5 months 33 months Well tolerated safety profile Perez K et al. IANS 2015; Abstract 23. 24
Axalimogene Filolisbac Monotherapy: Phase 2 FAWCETT Study in Anal Cancer Persistent/recurrent, loco-regional metastatic anal cancer Received at least one line of therapy for their metastatic disease or progressed after platinum-based therapy Stage 1 N = 31 Axalimogene Filolisbac monotherapy Every 3 weeks for up to 2 years Interim Analysis If 10% ORR or 20% 6-month PFS Two-stage Trial Design Stage 2 N=24 additional patients Axalimogene Filolisbac monotherapy Every 3 weeks for up to 2 years Endpoints Primary: Best overall response 6-month PFS Other: Safety and tolerability Duration of response Overall survival 25
ADXS-PSA ± KEYTRUDA (pembrolizumab) Phase 1/2 in Metastatic Prostate Cancer Inclusion Criteria: Pretreated metastatic CRPC <3 prior systemic treatment regimens or >1 prior regimen in the metastatic setting In collaboration with: WEEK 1 WEEK 4 WEEK 7 REPEAT Q 12 WEEK CYCLES Part A (n=21) ADXS-PSA Monotherapy Dose escalation (3 dose levels) Endpoints: To determine safety and RP2D ADXS-PSA ADXS-PSA ADXS-PSA Up to PD or 2 years WEEK 1 WEEK 4 WEEK 7 REPEAT Q 12 WEEK CYCLES Part B (n=30) ADXS-PSA ADXS-PSA ADXS-PSA ADXS-PSA + pembrolizumab Dose determination and confirmation Endpoints: To determine safety and RP2D of the combination Pembrolizumab Pembrolizumab Pembrolizumab Up to PD or 2 years NCT02325557 26
ADXS-HER2: Phase 1B Monotherapy in Multiple HER2-Expressing Tumors Primary Efficacy Endpoint: Safety and RP2D Primary endpoints: Safety and RP2D ADXS-HER2 Monotherapy Tumors to include: osteosarcoma, breast, gastric, and other cancers N 18 (dose finding); N 80 (expansion phase in tumorspecific subgroups) HER2-positive solid tumor Disease progressed or intolerant to standard therapy ECOG performance status 0 1 Total N ~100 3 WEEKS 3 WEEKS 3 WEEKS UP TO PD OR 2 YEARS 3+3 phase 1 design with possible expansion phase in up to 4 different indications ADXS-HER2 Day 0 ADXS-HER2 Day 21 ADXS-HER2 Day 42 If no DLT, next dose level initiates Pediatric osteosarcoma study planned in 2017 with: PD, progressive disease. https://clinicaltrials.gov/ct2/show/nct02386501 27
Financial Summary / Leadership Accountability Cash Summary Equity Summary Voluntary, Biweekly At- Market Equity Purchases (1) Cash on hand as of January 31, 2017 $136,861,985 Basic Shares Outstanding ( as of January 31, 2017) 40,057,067 Gross $ net shares Daniel J. O'Connor $794,369 150,437 No Debt Warrants and Options W=3,110,575 O=3,897,558 R=1,111,059 Robert G. Petit $172,105 32,237 Sara M. Bonstein $135,064 29,856 Fully Diluted Shares Outstanding 48,176,259 Management voluntarily purchases restricted stock directly from the Company every two weeks at market price (1) As of March 3, 2017 Represents RSU awards & share purchases only. Does not include options and/or warrants. 1
Upcoming Milestones Asset Axalimogene Filolisbac Targeted Indication Planned* Data/Event (estimated timing) Cervical GOG-0265 full data presentation (2017) Filing of GOG-0265 with EU (2017) Ph 3 HRLA cervical AIM2CERV enrollment update (ASCO 2017*) Axalimogene Filolisbac + durvalumab cervical/head & neck updated data (2017) Initiate Phase 3 study in metastatic cervical cancer (2017) Anal Ph 2 BrUOG 11 patients update (ASCO 2017*) FAWCETT Stage 1 data (2017) FAWCETT Begin Stage 2 (2017) Head & neck Mt Sinai/Baylor Ph 2 Head & Neck (ASCO 2017*) ADXS-PSA Prostate Preliminary data from ADXS-PSA + pembrolizumab cohorts A + B (2017) ADXS-PSA + pembrolizumab complete enrollment of expansion cohort (Q4 2017); preliminary data (2018) ADXS-HER2 Multiple cancers COG study in pediatric osteosarcoma study start (2017) Preliminary Phase 1 data (ASCO 2017*) ADXS-NEO Multiple cancers IND Accepted (March 2017) ADXS-HOT Multiple cancers IND filed (2017) *Depending on acceptance by medical conference. 29
APPENDIX January 2017
Lm Technology Overview: Harnessing Unique Life Cycle of Lm in APCs Lm-LLO agent taken up only by phagocytic dendritic cells/apcs Some Lm-LLO is killed and degraded within the phagolysosome Lm-LLO stimulates a strong innate multipathway immune response (eg. STING) in APC Lm-LLO expresses LLO-TAA fusion protein, which is processed by stimulated APC and activates TAA-specific T-cells Robust T-cell response generated toward TAA, allowing tumor-specific immune response Lm-LLO is phagocytose d by APC Some Lm-LLO escapes the phagolysosome and enters the cytosol Peptide-MHC complexes on the APC simulate CD4+ (MHC II) and CD8+ (MHC I) T cells Immune activation can overcome checkpoint inhibition and negative regulators of cellular immunity tllo-taa fusion protein is degraded by proteasomes into peptides for presentation to the MHC class I pathway APC, antigen-presenting cell; Lm, Listeria monocytogenes; MHC, major histocompatibility complex; TAA, tumor-associated antigen; tllo, truncated listeriolysin O. 31
ADXS-NEO: Leveraging Versatile Bacterial Vector System to Target Patient-specific Neoantigens tllo-taa fusion protein is a synthetic peptide presenting multiple neoantigens secreted into the cytoplasm of the APC 80 100 plasmid copies per bacteria Payload for 20 25 neoantigens per construct Multiple constructs can be administered for larger numbers of neoantigens Larger Bandwidth and Feasible Process Bandwidth: For example, 5 constructs could present 100 125 tumor neoantigens to T cells, obviating the need for a predictive algorithm Feasibility: Affordable and easy to manufacture in time for patient treatment (compare to autologous therapy) 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 peptides Decreases Tregs and MDSCs in the tumor microenvironment Lm, Listeria monocytogenes; TAA, tumor-associated antigen; tllo, truncated listeriolysin O. 32
Phase 2 Window of OpportunityStudy: Lm Technology Mechanism Validated, Impact on Tumor Microenvironment, Tregs Demonstrated Window of Opportunity Study Increase in CD8+ T Cells and Decrease in PD-L1 Axalimogene Filolisbac - 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 Axalimogene Filolisbac -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 Increase in Lymphocyte Infiltration preadxs postadxs Tumor-host interface Tumor-host interface Krupar R, et al. Presented at AACR 2016. Abstract LB-095. 33
GOG 0265: Objective Response Rates Investigator assessment of tumor best response Tumor best response, n (%) Stage 1 (N=26) Stage 2* (N=24) Overall (N=50) CR 0 (0) 1 (4) 1 (2) SD 7 (27) 8 (33) 15 (30) PD 10 (38) 11 (46) 22 (44) NE 6 (23) 4 (17) 10 (20) Missing post-baseline scan 3 (12) 3 (6) * These data represent initial Stage 2 results; Stage 2 is being re-enrolled after a clinical hold halted dosing in the first group of Stage 2 enrollees. CR, complete response, NE, no evaluation; PD, progressive disease, SD, stable disease. Huh W, et al. Presented at ASCO 2016 34
Axalimogene Filolisbac + Durvalumab Demonstrate Safety Profile Consistent with Previous Safety Findings with Manageable AEs All AEs All Patients n = 11 (%) 3 mg/kg Axalimogene Filolisbac n = 5 (%) 10 mg/kg Axalimogene Filolisbac* n = 6 (%) DLT - - - SAE 6 (55) 1 (20) 5* (83) AE 11 (100) 5 (100) 6 (100) AE leading to treatment DC 1** (9) - 1** (17) Deaths Treatment-related AEs 4 (36) (all due to PD) 1 (20) 3 (50) SAE 2 (18) - 2 (33) AE 10 (91) 5 (100) 5 (83) Grade 1 7 (64) 3 (60) 4 (67) Grade 2 6 (55) 3 (60) 3 (50) Grade 3 3 (27) 1 (20) Rigors and/or chills 2 Grade 4 1 (9) - DC, discontinuation; PD, progressive disease; WBC, white blood cell. *n = 1 patient who received durvalumab alone. **Grade 3 diarrhea. Axalimogene Filolisbac and/or durvalumab related. 2 (33) Rigors and/or chills, WBC, diarrhea, shortness of breath 1 (17) Hypotension 35
Axalimogene Filolisbac in Head & Neck Cancer: Window of Opportunity Study Purpose Determine immunogenicity Evaluate tolerability, safety, toxicity Determine HPV E6/E7-specific CD8+ CTL responses in blood Patient Population Study Design Newly diagnosed HPV+ squamous cell carcinoma of Stage I-IV of the oropharynx and is eligible to undergo treatment with transoral robotic surgery Non-randomized, single-arm phase 2 trial of neo-adjuvant Axalimogene Filolisbac treatment before standard of care transoral robotic surgery 2 doses of 1 10 9 cfu (33 days pre- and 14 days post-surgery) as 250ml infusion over 60 minutes Enrollment: 22 treated, plus 10 untreated control patients Preliminary Data Summary (Late Breaking Data at AACR) Detection of E6 and/or E7 specific T-cell response in peripheral blood in 5 of 8 treated patients Potential Axalimogene Filolisbac-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 Increase in CD8+ T-Cells and Decrease in PD-L1 36
Synergy with Checkpoint Inhibitors and Co-Stim Molecules: AXAL & PD-1, GITR, OX-40 % Survival Mouse HPV Tumor Model: Combination Studies AXAL + PD-1* AXAL + GITR AXAL + OX-40 Days after tumor implantation Preclinical rationale for checkpoint and co-stim combination trials *Data published in Journal for ImmunoTherapy of Cancer 2013, 1:15 doi:10.1186/2051-1426-1-15 37
Combining Sub-therapeutic AXAL with anti-cd137 mab or anti- CTLA4 mab enhanced tumor control and prolonged animal survival T u m o r V o m e (m m 3 ) Tumor volume (mm 3 ) P e r c e n t s u r v a l Percent survival B 2 0 0 0 PBS AXAL* + isotype control AXAL* + anti-cd137 ( 300 µg) AXAL* + anti-ctla-4 (50 µg) C 1 0 0 8 0 PBSN T A X A L + o p e c o n l AXAL* + isotype control A X A L + a n D 1 3 7 3 0 0 u g AXAL* A X A+ L + anti-cd137 a n ti-c T L A 4 5( 0 u300 g µg) AXAL* + anti-ctla-4 (50 µg) 1 5 0 0 6 0 1 0 0 0 4 0 5 0 0 0 * * * *P <.05 * * * 1 0 1 5 2 0 2 5 3 0 D a y s p o s t m o r im p n tio n Days after tumor implantation 2 0 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 Days a y s p oafter s t tu mtumor o r im p laimplantation n tio n **** **** ****P <.0001 * sub-therapeutic dose of Axal to demonstrate synergy Kosoff et al, SITC 2016 38
Onsite Manufacturing Fully integrated in-house development, manufacturing, and testing construction build-out in 2016 In-house CGMP, flex-space Process-development suite Solution preparation Inoculum preparation Bulk drug substance manufacturing Bulk drug product manufacturing Packaging NEO manufacturing QC labs Warehouse storage and 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 39