jefferies 2015 healthcare conference › cmsfiles › jefferies.com › files › advaxis.pdf ·...

Jefferies 2015 Healthcare Conference

2015 Advaxis, Inc. | www.advaxis.com

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 as to

the anticipated timing of clinical studies and other business developments, statements regarding the

safety and efficacy of Advaxis’s product candidates, statements as to the development of new

constructs, expectations as to the adequacy of our cash balances to support our operations for

specified periods of time and as to the nature and level of cash expenditures, expectations as to

market opportunities, our ability to take advantage of those opportunities, and 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, 2014, available at http://www.sec.gov.

The Company 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 Company Overview

Background

• Lab, office and vivarium located in Princeton, NJ

• Core technology – bacterial vector, Listeria monocytogenes (Lm), engineered with unique

fusion protein, truncated listeriolysin O (tLLO) and select tumor-associated antigens

(TAAs), exclusively licensed worldwide from University of Pennsylvania

ADXS Snapshot

• Raised ~ $140M since October, 2014

• Leadership team with established track record of success

• Fully-diluted market cap based on TSM: $694M (as of 5/18/15)

• Cash: $30.6M (as of 1/31/2015) + $23M in registered direct (on 2/18/2015) + $61M in follow-on

offering & shoe (on 5/5/2015 & 5/20/2015)

Summary of Strengths

• Highly proprietary technology (80+patents) with low royalty obligation (2.5%)

• Industry interest in technology as evidenced by existing collaborations

• Oncology focused – 4 Orphan Drug Designations including lead indications

• Straightforward and scalable manufacturing process

3


Experienced Management Team

4

Gregory Mayes Chief Operating Officer

Daniel O’ConnorChief Executive Officer

David Mauro, MD, Ph.D.Chief Medical Officer

Robert Petit, Ph.D.Chief Scientific Officer

Chris French, MBAVP, Compliance

Sara Bonstein, MBA Chief Financial Officer

Mayo PujolsVP, Manufacturing

All trademarks and logos are the property of their respective owners.

Fred FrulloVP, Regulatory

Tom HareVP, Clinical Operations


Key Value Drivers

Proprietary Lm Technology™

• Live attenuated bacteria stimulates the immune system to view tumor as bacterial infected

cell marked for elimination

• Alters tumor microenvironment by increasing tumor fighting cells and decreasing tumor

protecting cells

Three Lm Technology™ Immunotherapy Candidates in Clinical Development

• ADXS-HPV – Comprehensive clinical development program in early and late stage HPV-

associated cancers

• ADXS-HER2 – PoC established / initiating clinical development in HER2 expressing solid

tumors

• Pending approval w/ USDA for canine osteosarcoma (licensed to Aratana)

• ADXS-PSA – Clinical development program in metastatic castration-resistant prostate

cancer (mCRPC) as monotherapy and in combination w/ KEYTRUDA® enrolling

Robust Pre-Clinical Pipeline

• Versatile platform could yield numerous Lm-LLO immunotherapy oncology product

candidates

KEYTRUDA is a registered trademark of Merck & Co., Inc.

HER2, human epithelial growth factor receptor 2; H&N, head and neck; HPV, human papilloma virus; PSA, prostate specific antigen.

5


Lm Technology™ Harnesses Unique Life Cycle of Lm in APCs

6

Lm-LLO being

phagocytosed

by APC

Lm-LLO escaping

from the

phagolysosome

Killing and degradation of

Lm-LLO within the

phagolysosome

Degradation of tLLO-TAA

fusion protein into peptides

for the MHC class I pathway

Peptide-MHC complexes

on the APC coming into

contact with appropriate

T Cell receptors


Lm Technology™

7

APC, antigen-presenting cell; CTL, cytotoxic T lymphocyte; LLO, listeriolysin O; Lm, listeria monocytogenes; MDSC, myeloid-derived

suppressor cell; TAA, tumor-associated antigen; tLLO, truncated LLO; TME, tumor microenvironment; Treg, T-regulatory cell

2015 Advaxis, Inc. | www.advaxis.com 8

Efficacy

Attributes

Safety

Attributes

IP

Attributes

• High expression and secretion of tLLO/ fusion protein (tumor

associated antigen [TAA])

• Efficacy as monotherapy (includes CR, PR and increased survival)

• No need for cyclophosphamide, GVAX or other preconditioning

agents to enhance therapeutic effect

• Impacts tumor microenvironment (TME) by disabling T-regs & MDSC

• High attenuation of ADXS-HPV with established safety

• Dosed up to 3.3x109 in humans with potential to go higher

• Predominantly Grade 1 and 2 AEs in 220+ patients treated to date

• No cases of lymphopenia

• ~1% Grade 3 AEs (no Grade 4-5)

• Exclusively in-licensed original IP from UPENN where Lm platform

was invented

• Any other Lm technologies must avoid infringing on this IP

• 80+ issued and 80+ pending patents worldwide for platform, product

candidates, methods, manufacture, process and formulation

Potential Advantages of Lm Technology™


Product Indication Phase 1 Phase 2 Phase 3

ADXS-HPV Cervical Cancer*

AIM2CERV – Adjuvant Randomized vs Placebo

Metastatic – Randomized vs Cisplatin/ADXS-HPV

Metastatic – GOG

Metastatic – Single Arm High Dose

Metastatic – Combo with MEDI 47361

Stage I-IIa – Combo with epacadostat (INCB24360) 2

Head and Neck Cancer*

Neoadjuvant – Window of Opportunity - Mount Sinai

Metastatic – Combo with MEDI 47361

Anal Cancer*

RTOG – Adjuvant Randomized vs Control

Adjuvant – Single Arm High Risk – Brown University (BrUOG)

Metastatic – Single Arm

1 Partnership with MedImmune (AZ)

2 Partnership with Incyte

* Orphan Drug Designation

Planned 2015Completed In Process

In Process = FDA accepted IND and/or ongoing trial

M Monotherapy

C Combination

M

C

M

C

M

Phase 3

Phase 2

Phase 2

Phase 1/2

Phase 1/2

Phase 2

Phase 2

Phase 1/2

Phase 1/2

Phase 2

Phase 2/3

Phase 1

Clinical Development: ADXS-HPV


Clinical Development: ADXS-PSA and ADXS-HER2

10

Product Indication Phase 1 Phase 2 Phase 3

ADXS-PSA Prostate Cancer

Metastatic – Combo with KEYTRUDA® 1(pembrolizumab)

ADXS-HER2 HER2-positive Solid Tumors (including Osteosarcoma*)

Metastatic – Single Arm

Pediatric Osteosarcoma (Planned with COG)

1 Partnership with Merck

* Orphan Drug Designation

M

C Phase 1/2

Phase 1

M

Planned 2015Completed In Process

In Process = FDA accepted IND and/or ongoing trial

M Monotherapy

C Combination

Phase 2


ADXS-HPV: Randomized Phase 2 Study –Recurrent Cervical CancerStudy Schema

11

Naproxen 500 mg BID (day -1, 0) and promethazine 25 mg BID (pre-dose 8 hours) administered as premedications

Ampicillin 500 mg QID (days 3-9) administered post-infusion

ADXS-HPV Monotherapy

1x109 cfu x 3 doses q 28 days

(days 0, 28, 56) as an 80 ml

infusion over 15 min

N = 56

Primary Efficacy Endpoint:

Overall Survival

AR

M A

AR

M B

ADXS-HPV + Cisplatin


(days 0, 88, 106, 134) as an 80

ml infusion over 15 min

Cisplatin 40 mg/m2 weekly x 5

(days 30, 37, 44, 51, 58)

N = 54

ADXS-HPV ADXS-HPV ADXS-HPV

ADXS-HPV

Month 1 Month 2 Month 3 Month 4 Month 5

ADXS-HPV ADXS-HPV ADXS-HPV

Cisplatin

Basu, ASCO 2014; Poster 5610


ADXS-HPV: Randomized Phase 2 Study –Recurrent Cervical CancerSafety Summary

12

109 patients received 264 doses of ADXS-HPV at 1x109 cfu’s (N=109)

Grade 1-2 AEs (76 patients reported) 41 (38%)

Chills/Shivering 41 (38%)

Flu Like Symptom 13 (12%)

Vomiting 6 (6%)

Nausea 5 (5%)

Fever 5 (5%)

Dizziness 2 (2%)

Cytokine Release Syndrome 1 (1%)

Headache 1 (1%)

Weight Decreased 1 (1%)

Blood Alkaline Phosphatase Increased 1 (1%)

Grade 3 AE (1 patient reported)

Fever 1 (1%)



ADXS-HPV: Randomized Phase 2 Study –Recurrent Cervical Cancer Survival Analyses at 12, 18 and >24 Months

Long-Term Survivors (LTS) in recurrent cervical cancer are rare

13

PatientsOverall

(N=109)

ADXS-HPV

ALONE

(N=55)

ADXS-HPV +

CISPLATIN

(N=54)

12-Month Survival32%

(35 / 109)

29%

(16 / 55)

35%

(19 / 54)

18-Month Survival22%

(24 / 109)

22%

(12 / 55)

22%

(12 / 54)

≥ 24-Month Survival 18%

(16 / 91*)

15%

(7 / 46)

20%

(9 / 45)

* >24 month survival rate is based on 16 known to be alive out of 91 patients from the OS efficacy population with at least 24 months of

documented follow-up data


Safety Summary:Grade 1-2 related adverse events (AE) were reported in 38% of patients, the most

frequent of which were chills and flu-like symptoms. One patient reported a Grade 3

related AE (fever).


ADXS-HPV: Open Label 2-Stage Phase 2 Study Recurrent Cervical Cancer (GOG 0265)

14

• N = ~67 (Stage 1 and 2)

• Persistent or recurrent cervical cancer

• > 1 prior chemotherapy regimen for metastatic disease,

excluding that received as a component of primary treatment

• GOG PS 0/1

• Measurable disease > 1 target lesion (RECIST 1.1)


12-month survival

ADXS-HPV Monotherapy


(month 1, 2, 3) as an 80 ml

infusion over 15 min

ADXS-HPV

Day 0

ADXS-HPV

Day 28

ADXS-HPV

Day 56

Month 2Month 1 Month 3

GOG, Gynecologic Oncology Group

https://www.clinicaltrials.gov/ct2/show/NCT01266460


ADXS-HPV: Open Label 2-Stage Phase 2 Study Recurrent Cervical Cancer (GOG 0265)Stage 1 Preliminary Data (March 2015)

15

* Recurrent or persistent metastatic carcinoma of the cervix has a 12-month survival rate of ~15%1,2

N = 29 enrolled

N = 6 on therapy

but < 12 month follow up

N = 7 reached

12-month survival (27%)

N = 13 off therapy with

< 12-month survival

N = 3 did not receive therapy

N = 26 treated

Safety: chills, rigors, flu-like symptoms

1. Tewari KS, Monk BJ. Curr Oncol Rep. 2005;7(6):419-34

2. L. Copeland Clinical Presentation, March 2015.

Met >20% efficacy threshold* and has proceeded to Stage 2 additional enrollment of n=37


“AIM2CERV” Planned Phase 3: CCRT vs. CCRT Combined with ADXS-HPV High-risk, Locally Advanced Cervical Cancer Patients

Company Confidential

R

A

N

D

O

M

I

Z

E

High Risk, Locally

Advanced Cervical

Cancer

Placebo IV

Cisplatin

(40mg/m2) and

Radiation

Therapy given

concurrently

(CCRT)

ADXS-HPV

(1 x 109 cfu)

Up to 1 yr

ADXS-HPV

(1 x 109 cfu)

Placebo IV

Up to 1 yr

Cisplatin

(40mg/m2) and

Radiation

Therapy given

concurrently

(CCRT)

Reference

Group

Treatment

Group

16

Randomization 1:2 between

Reference and Treatment

Groups


ADXS-HPV + Mitomycin, 5-FU, & Radiation: Open Label Phase 1/2 Study Anal Cancer (BrUOG)

17

BrUOG, Brown University Oncology Group

• N = 25

• Primary stage II-III anal cancer

• High risk of recurrence

• HPV-positive

ADXS-HPV

1x109 cfu x 4 (1 prior to chemoRT and 3 post, q 28 days)

as a 500 ml infusion over 30 min

ADXS-HPV #1

Day -10 to 14

Mito/5-FU

ADXS-HPV #2

Day +10 post IMRT

6 weeks IMRT 28 days


6-month CR-rate

Mito/5-FU

28 days Follow up

ADXS-HPV #3 ADXS-HPV #4

Bio

psy

Bio

ps

y

https://www.clinicaltrials.gov/ct2/show/NCT01671488

Perez K et al. IANS 2015; Abstract 23


ADXS-HPV + Mitomycin, 5-FU, & Radiation: Open Label Phase 1/2 Study Anal Cancer (BrUOG)Preliminary Data

18

Study open: April 2013

N = 10 / 25 patients enrolled

Efficacy Summary as of March 2015:

• 10 patients received study treatment

• All patients who have completed treatment achieved CR

• No patient has developed recurrence

• Historical 3-year recurrence rate in similar patient

population = ~45%

• Follow-up range: 0.5 months – 24 months

Safety Summary as of March 2015:• Chills, occasional rigors, flu-like symptoms) resolved prior to

leaving clinic (~2 hours)

Perez K et al. IANS 2015; Abstract 23.


NRG/RTOG Planned Phase 2/3: CCRT vs. CCRT Combined with ADXS-HPV High-risk, Locally Advanced Anal Cancer Patients

Company Confidential

R

A

N

D

O

M

I

Z

E

High Risk, Locally

Advanced Anal Cancer

Placebo IV

Mitomycin C +

5FU and

Radiation

Therapy given

concurrently

(CCRT)

ADXS-HPV

(1 x 109 cfu)

Up to 1 yr

ADXS-HPV

(1 x 109 cfu)

Placebo IV

Up to 1 yr

Mitomycin C +

5FU and

Radiation

Therapy given

concurrently

(CCRT)

Reference

Group

Treatment

Group

19

Study design is currently being proposed to NCI CTEP


ASCO 2015 ADXS-HPV Poster Presentations

20

Poster Session: Ghamande S, et al.

Saturday, May 30, 2015

8:00 – 11:30 am, S Hall A

Abstract# TPS3096, Poster Board# 417b

Poster Session: Miles B, et al.

Saturday, May 30, 2015

1:15 – 4:45 pm, S Hall A

Abstract# TPS6088, Poster Board# 409b


ADXS-HER2: Open Label Phase 1 StudyCanine Osteosarcoma UPENN School of Veterinary Medicine

21

• N = 18 dogs

• Canine osteosarcoma (OSA)

• Post amputation and chemotherapy

ADXS-HER2

4 dose levels tested:

2x108 cfu

5x108 cfu

1x109 cfu

3x109 cfu Diagnosis &

Amputation

Carboplatin q21 days

x 4 doses

Study Goals:

• Identify MTD

• Safety

• Tumor-specific immunity

• Prevention of metastases

• Prolongation of survival

UPENN, University of Pennsylvania

ADXS-HER2 #1, #2, #3

Screening Visit

Standard Treatment

* Paolini M., BMC Genomics, 2009


ADXS-HER2: Open Label Phase 1 StudyCanine Osteosarcoma UPENN School of Veterinary Medicine

ADXS-HER2 Dose 2x108 5x108 1x109 3x109 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

# Pet Dogs with Treatment Related Adverse Events

(All toxicities reported are Grade 1)

ADXS-HER2 and Overall Survival

Median survival: Case-matched control: 316 days

ADXS: not yet reached

22

Survival of Data 11:Survival proportions

0 200 400 600 800 10000

20

40

60

80

100

VACCINE

Control

Days from diagnosis

Pe

rce

nt s

urv

iva

l

p<0.0001

n=18


0 200 400 600 800 10000

20

40

60

80

100

VACCINE

Control

Days from diagnosis

Pe

rce

nt su

rviv

al ADXS-HER2

n=11

2 dogs censored from ADXS arm, deaths unrelated to OSA

Next Steps: Pending approval USDA for veterinary use; Currently under investigation in combination with RT in OSA


ADXS-HER2: Combination with Radiation in Untreated Canine Osteosarcoma

23

2 x 8Gy

0 100 200 300 4000

20

40

60

80

100

Days

Pe

rce

nt s

urv

iva

l

Pe

rce

nt su

rviv

al

Time (days) Time (days)

n=10

2 x 8Gy + ADXS31-164

Pe

rce

nt

su

rviv

al

n=57


0 100 200 300 4000

20

40

60

80

100Legend

TTP (days)

Pro

gre

ssio

n fre

e s

urv

iva

l

2 x 8Gy + ADXS31-164

n=10

Pro

gre

ssio

n fre

e s

urv

iva

l

Time (days)

Historical Perspective:Knapp-Hoch et al. J Am Anim Hosp Assoc. 2009 Jan-

Feb;45(1):24-32.

Radia

tion a

lone

Rad

iation p

lus

AD

XS

-HE

R2

Median TTP = 221 daysMedian OS = 285 days

ADXS-HER2 and Radiation: N = 10 pet dogs with untreated primary OSA

2 x 8Gy

0 100 200 300 4000

20

40

60

80

100

Days

Pe

rce

nt s

urv

iva

l

Pe

rce

nt su

rviv

al

Time (days) Time (days)

n=10

2 x 8Gy + ADXS31-164

Pe

rce

nt

su

rviv

al

n=57


0 100 200 300 4000

20

40

60

80

100Legend

TTP (days)

Pro

gre

ssio

n fre

e s

urv

iva

l

2 x 8Gy + ADXS31-164

n=10

Pro

gre

ssio

n fre

e s

urv

iva

l

Time (days)

S urvival of D ata 2 :S urvival p rop o rtio n s

0 100 2 00 3 00 400

0

2 0

40

6 0

80

100

Legen d

T TP (days )

Progression free survival

0 100 2 00 3 00 400 5 00

0

2 0

40

6 0

80

100

D ays

Percent survival

n=10

n=10

ADXS-HER2ADXS-HER2

00

20

40

60

80

100

20

40

60

80

100

0 100 200 300 400100 200 300 400

Mason N et al. AACR 2015; Abstract LB-113

Median OS = ~120 days (expected OS range for dogs that cannot undergo

amputation and receive only palliative radiation

and analgesics is 3 - 5 months)


ADXS-HER2: Phase Ib Dose-Escalation Study in HER2 Expressing Solid Tumors

24

• N < 18 (Dose finding); N < 80 (Expansion phase) [Total N ~100]

• HER2-positive solid tumor (>1+ positivity in 1% of cells by IHC)

• Disease progressed or intolerant to standard therapy

• ECOG PS 0-1

• 3+3 Phase I Design

Primary Endpoint:

Safety and RP2 Dose

ADXS-HER2 Monotherapy

Dose level 1: 1x109 cfu q 3 wks



ADXS-HER2

Day 0

ADXS-HER2

Day 21

ADXS-HER2

Day 42

3 weeks3 weeks 3 weeks

PD, disease progression; RP2, Recommended phase 2

Up to PD

or 2 years

If no DLT, next

Dose level initiates

https://clinicaltrials.gov/ct2/show/NCT02386501


ADXS-PSA: Phase 1-2 Dose Escalation and Safety Study Alone and Combined with Pembrolizumab

25

ADXS-PSA Monotherapy Dose level 1: 1x109 cfu d1 wk 1,4,7 q12 wks

Dose level 2: 5x109 cfu d1 wk 1,4,7 q12 wks

Dose level 3: 1x1010 cfu d1 wk 1,4,7 q12 wks

N = 21PA

RT

AP

AR

T B ADXS-PSA + Pembrolizumab

ADXS-PSA Part A Dose –DL1

d1 wk 1,4,7 q12 wks

Pembrolizumab 200 mg

d1 q 3wks in 12 wk cycles

N = 30

ADXS-PSA ADXS-PSA ADXS-PSA

Week 1 Week 4 Week 7 Repeat q 12 week cycles

• N = 21 (Part A); N = 30 (Part B) [Total N = 51]

• Pretreated metastatic castration-resistant prostate cancer (CRPC)

• No more than 3 prior lines of systemic therapy (<1 chemotherapy)

• mTPI Design (Part A) RP2 Dose

• Part B ADXS-PSA Dose = Part A RP2 DL-1 + pembrolizumab

ADXS-PSA ADXS-PSA ADXS-PSA

Up to PD

or 2 years

Up to PD

or 2 years

https://clinicaltrials.gov/ct2/show/NCT02325557


Synergistic Combinations May be the Future: ADXS-HPV & PD-1 Checkpoint Inhibitor

26

Pe

rce

nt

Su

rviv

al

Days after tumor implantation

Treatments:

Lm-LLO-E7: 5x106 cfu

CT-011 mAb: 50 μg

TC-1 tumor

implantation Tx 1 Tx 2

Data published inJournal for ImmunoTherapy of

Cancer 2013, 1:15 doi:10.1186/2051-1426-1-15

0 8 15

Days

HPV Tumor Model

Low dose Lm-LLO immunotherapy can be combined with a checkpoint inhibitor


Synergistic Combinations May be the Future:ADXS-HPV & Anti-GITR or Anti-OX40

Lm-LLO immunotherapy can be combined with agonistic antibodies to

immune co-stimulatory molecules

27

ADXS-HPV + Anti-GITR ADXS-HPV + Anti-OX40

HPV Tumor Model


Novel Combination Therapy Collaborations

28

Entered into an R&D Collaboration with

July 2014

Phase 1/2 study evaluating the safety and efficacy of ADXS-PSA in

combination with KEYTRUDA® (pembrolizumab) (anti-PD-1)

August 2014


Phase 1/2 study evaluating the safety and efficacy of ADXS-HPV in combination with MEDI4736

(anti-PD-L1)

February 2015


Phase 2 study evaluating the safety and efficacy of ADXS-HPV

as a monotherapy and in combination with INCB24360

(epacadostat) (IDO1)

May 2015


Evaluation of Lm-LLO immunotherapies plus

antibodies targeting GITR, OX40, LAG-3 and TIM-3


Strategic, Value-Building Opportunities

• Combinations: Exploit construct potential

by combining our Lm technology with

best-in-class therapies to investigate

potentially improved efficacy

• CarT

• GITR

• OX40

• Other co-stimulatory modalities

• Positioning: Establish potential of

Advaxis immunotherapies in clinic trials

and then license product candidates to

market dominant companies

29

BD Objectives Licenses

• License (Development &

Commercialization)

• ADXS-HER2 (animal health)

• Canine osteosarcoma + 3

additional products

• Exclusive License (India and

emerging markets)

• ADXS-HPV

• HPV-associated cervical cancer

• Exclusive License (Asia)

• ADXS-HPV

• HPV-associated cancers


Platform Versatility

Advaxis has developed several product constructs leveraging the company’s platform technology

Lm-LLO +

Single Antigen Constructs

SurvivinLymphoma

Pre-Vet

PSCAProstate Cancer

Pre-Clinical

HMW-MAALymphomaPre-Clinical

WT-1Several (Pan)Pre-Clinical

CEAOvarian

Pre-Clinical

CA9Renal and Others

Pre-Clinical

VEGF-r2Solid TumorsPre-Clinical

P53Breast CA

Pre-Clinical

IL13RA2Solid TumorsPre-Clinical

FAPBreast CA

Pre-Clinical

SCCE-KLK7Ovarian, others

Pre-Clinical

ISG 15Bladder

Pre-Clinical

Endoglin (CD-105)

Breast CAPre-Clinical

30

https://www.google.com/url?q=http://en.wikipedia.org/wiki/WT1&sa=U&ei=JW5FU7LlNKPg2AWnl4DIAQ&ved=0CC4Q9QEwAA&usg=AFQjCNH9XRTOHKIHTKZpomzOMp0tZbDbHA

https://www.google.com/url?q=http://en.wikipedia.org/wiki/WT1&sa=U&ei=JW5FU7LlNKPg2AWnl4DIAQ&ved=0CC4Q9QEwAA&usg=AFQjCNH9XRTOHKIHTKZpomzOMp0tZbDbHA

https://www.google.com/url?q=http://www.uscnk.com/directory/Carcinoembryonic-antign(CEA-CD66)-0150.htm&sa=U&ei=um5FU6T0GYPi2QXR7IDACQ&ved=0CFQQ9QEwEw&usg=AFQjCNFwTmJr3_XMMNe1CBSDvnUsbKST1w

https://www.google.com/url?q=http://www.uscnk.com/directory/Carcinoembryonic-antign(CEA-CD66)-0150.htm&sa=U&ei=um5FU6T0GYPi2QXR7IDACQ&ved=0CFQQ9QEwEw&usg=AFQjCNFwTmJr3_XMMNe1CBSDvnUsbKST1w

https://www.google.com/url?q=http://en.wikipedia.org/wiki/Carbonic_anhydrase_9&sa=U&ei=sIRFU7X3MOje2QWv8oCACg&ved=0CC4Q9QEwAA&usg=AFQjCNGHs7EPiKsrOvE8Jf6lNEvPaN3_ig


http://en.wikipedia.org/wiki/File:PDB_1a1u_EBI.jpg

http://en.wikipedia.org/wiki/File:PDB_1a1u_EBI.jpg

https://www.google.com/url?q=http://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha&sa=U&ei=SIhFU7GOH-br2QWyoYEI&ved=0CDoQ9QEwBg&usg=AFQjCNGiTLeFzUD5QmjeVM56be6GoJDu7g

https://www.google.com/url?q=http://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha&sa=U&ei=SIhFU7GOH-br2QWyoYEI&ved=0CDoQ9QEwBg&usg=AFQjCNGiTLeFzUD5QmjeVM56be6GoJDu7g

https://www.google.com/url?q=https://www.stage1diagnostics.com/products/biomarkers/klk7&sa=U&ei=0ohFU4nKGMKC2QWL0oCgCQ&ved=0CC4Q9QEwAA&usg=AFQjCNGibTWuAKHUM7SOS7ZhQqbTwngRSg

https://www.google.com/url?q=https://www.stage1diagnostics.com/products/biomarkers/klk7&sa=U&ei=0ohFU4nKGMKC2QWL0oCgCQ&ved=0CC4Q9QEwAA&usg=AFQjCNGibTWuAKHUM7SOS7ZhQqbTwngRSg

https://www.google.com/url?q=http://en.wikipedia.org/wiki/ISG15&sa=U&ei=jolFU9aOKYb42AW804CQDw&ved=0CFYQ9QEwEw&usg=AFQjCNHotf69Xm6nJrIts4UdYgcDXyTNiQ

https://www.google.com/url?q=http://en.wikipedia.org/wiki/ISG15&sa=U&ei=jolFU9aOKYb42AW804CQDw&ved=0CFYQ9QEwEw&usg=AFQjCNHotf69Xm6nJrIts4UdYgcDXyTNiQ


Financial Summary

Cash Summary

• Cash as of January 31, 2015

$30.6M

• Cash receivables since Jan ‘15

$23.0M – February Registered

Direct Offering

$61.2M – Follow-on Offering &

Shoe (May)

• Capital raised since October ‘13

~$140M

• No Debt

Equity Summary

• Basic Shares Outstanding

29.9M (as of 5/5/2015)

• Warrants and Options*

4.1M and 0.5M

• Pro-forma Fully Diluted

33.2M

* As of 1/31/2015


Leadership Accountability

Gross $ net shares vested unvested

Daniel J. O'Connor $630,884 152,007 107,543 100,000

David J. Mauro $39,665 5,938 32,884 151,333

Gregory T. Mayes $171,910 26,663 36,845 75,000

Robert G. Petit $119,821 28,065 43,409 63,319

Sara M. Bonstein $90,956 26,086 34,530 33,333

(1) Above figures are as of May 1, 2015

Out of Pocket Funds (1) Company Incentive Awards (1)

Management voluntarily purchases restricted stock directly from the Company every two weeks at market price


Anticipated Milestones

33

Programs Event Timing

ADXS-HPV Initiate Phase 1/2 combination studies w/ MEDI4736 in cervical and

H&N cancers

Mid 2015

Initiate Phase 2 Stage I-IIa combination study w/ IDO1 epacadostat

(INCB24360) in cervical cancer

H2 2015

Stage 1 12 month overall survival results for Phase 2 monotherapy

study in cervical cancer (GOG 0265)

H2 2015

File SPA & initiate randomized Phase 3 monotherapy study in cervical

cancer

H1 2015

Initiate Phase 2 single arm metastatic monotherapy study in anal

cancer

H2 2015

Initiate randomized pivotal Phase 2/3 monotherapy study in adjuvant,

locally-advanced metastatic anal cancer (NRG/RTOG)

H1 2016

ADXS-HER2 Initiate Phase 1 single arm monotherapy study in solid tumors Mid 2015

Initiate Phase 2 study in pediatric osteosarcoma (COG) H1 2016

ADXS-PSA Complete enrollment of Stage 1 Phase 1/2 combination study w/

KEYTRUDA® in prostate cancer

H2 2015

Other Lm

Candidates

Potential BD monotherapy deal and clinical combination collaborations Throughout 2015


305 College Road East, Princeton, NJ

www.advaxis.com

[email protected]


APPENDIX

35


Experienced Management Team and Board of Directors

36

Management Team

Daniel J. O’Connor, Esq. President, Chief Executive Officer• 15 years of executive, legal, regulatory, compliance, manufacturing, and quality experience in

the biopharmaceutical industry

• Former Senior VP and General Counsel of ImClone Systems, Inc.

• Played a key role in development, licensing, and commercialization of Erbitux®

David Mauro, MD, Ph.D. Executive Vice President, Chief Medical Officer• 15 years experience in oncology drug development

• Executive Director, Section Head Oncology Clinical Development at Merck & Co., involved in

oversight and implementation for multiple programs, including Keytruda®

Gregory Mayes Executive Vice President, Chief Operating Officer• 20 years experience in operations and bio-pharmaceuticals, Executive Committee for

Dendreon Corp., President, Unigene Laboratories, VP, GC, Chief Compliance Officer,

ImClone Systems Inc., Senior Counsel, AstraZeneca Pharmaceuticals

Robert Petit, Ph.D. Executive Vice President, Chief Scientific Officer• 25 years experience in oncology drug development

• U.S. medical strategy lead for Yervoy® program at Bristol-Myers Squibb (NYSE: BMY) as the

Director of Medical Strategy for oncology products and Director of Global Clinical Research

Sara Bonstein Senior Vice President, Chief Financial Officer• 10 years of financial leadership experience in the life sciences industry with Eli Lilly &

Company, ImClone Systems, and Johnson & Johnson

Chris French Vice President, Regulatory and Medical Affairs• 20 years experience in drug development, including medical affairs, regulatory affairs,

business development, and scientific communications

• U.S. Director of Oncology Scientific Communications for Bristol-Myers Squibb

Mayo Pujols Vice President, Manufacturing• Former Executive Director, Technical Operations for Merck, Sharp & Dohme (MSD)

• 7 years at MedImmune most recently as Director Clinical Manufacturing Operations, R&D

Board of Directors

David Sidransky, MD• Co-Founder and Chairman, Champions Oncology

• Professor, Johns Hopkins, Oncology Medicine

Samir Khleif, MD• Director, GRU Cancer Center

• Former Chief of the Cancer Vaccine Section,

National Cancer Institute (NCI)

James Patton, MD, MBA Chairman• VP, Millennium Oncology Management

• Founder and Chairman, VAL Health

Roni A. Appel• Managing Director, LibertyView Equity Partners

Richard Berman• Former CEO, Easylink Services

• Former SVP, Bankers Trust Company

• Director, Lustros, Inc., and Neostem, Inc.

Thomas McKearn, MD• Founder, Cytogen Corporation

Daniel J. O’Connor, Esq.• President & CEO, Advaxis


Powerful Innate Immunity• Live Vector serves as multiple adjuvants

• Expresses multiple PAMPs

• Activates external and internal TLRs and NOD-

like proteins• (TLRs 1, 2, 5, 6, NOD-1, NOD-2, CpG, LLO is a

PAMP)

• Triggers STING receptor within APC

• Creates TH-1 “Immunotype”

Access to APCs (circulating and tissue-based)

• Facilitated phagocytosis by dendritic cells and

APCs

• Escapes phagolysosome via LLO

• Replicates and secretes gene products within

cytoplasm of APC

• Bridges innate and adaptive immunity

Advaxis Constructs Secrete Fusion Protein:

tLLO-TAA within APC• “Programs”APCs in situ within each patient

No Neutralizing Antibodies – Suitable for

Repeat Administration

Adaptive Immunity• Cross presents to MHC I and II pathways

• Matures and activates dendritic cells

• Drives CTL-focused immune response in context of

“perceived” listeriosis.

• Reveals “hidden” CTL epitopes

• Induces PD-1 / PD-L1 expression

• Bypasses immune checkpoints

Changes Tumor Microenvironment• Specifically breaks tolerance within tumors

• Chemokines facilitate infiltration of CD4+ and CD8+

T-cells, myeloid-derived suppressor cells (MDSCs)

• Reduces and disables Tregs, reduces and disables

MDSCs

• Antigen spreading observed

Directly Invades Tumors• Redirects Listeria specific killing

• Directly kills tumor cells by apoptosis

Vector Can Be Cleared with Antibiotics

37

CTL, cytotoxic T-cell lymphocytes; NOD, nucleotide-binding oligomerization domain; PAMP, pathogen-associated molecular pattern; PD-1/PD-L1,

programmed death- and programmed death ligand-1;, TH-1, T helper type 1;TLR, toll-like receptor; Tregs, T-regulatory cells.

Favorable System for a Cellular Immune Response


Unique Advantages of the Advaxis Lm-LLO Manufacturing Platform

38

• Simple, scalable, and robust process

• Uses standard biotech operations and assays

• Commercial process & equipment equivalent to pilot scale

• Simplifies technology transfer, scale-up & manufacturing operations

• Ensures RFT manufacturing

• Closed system ensures sterility

• Single-use technology applied throughout the process

• Reduces capital investment

• Eliminates numerous cleaning & sterilization steps

• Enables local manufacturing in emerging markets

• High throughput process and yield

• Short lead times (~50% shorter than typical live virus vaccines) allow earlier

delivery of products

• Ability to freeze bulk drug substance or proceed with straight-thru processing to

filling operations

• Flexible storage conditions and cold chainRFT, Right First Time


ADXS-HPV: Randomized Phase 2 Study –

Recurrent Cervical Cancer

Tumor Response Waterfall Plot

39

-100-90-80-70-60-50-40-30-20-10

0102030405060708090

100110120130140150160170180190200210220230240250260270280290300310320330340350360370380390400410420430440450

10

70

08

10

00

08

12

10

06

11

60

03

11

00

16

10

90

04

10

90

09

10

50

07

12

80

01

10

70

03

10

10

07

11

00

12

11

00

17

10

40

03

12

40

11

11

60

07

11

10

05

10

40

06

12

10

01

10

70

06

10

30

09

12

80

02

10

70

07

11

00

10

10

40

08

10

70

05

11

30

01

11

10

01

11

50

04

10

30

13

11

20

05

12

60

01

11

30

10

11

00

08

10

40

01

10

00

19

10

40

05

10

70

09

11

10

06

11

50

08

11

60

06

10

00

04

11

00

04

11

00

03

12

10

07

10

00

11

10

50

09

10

70

02

10

10

06

10

00

15

10

30

15

12

10

02

10

10

08

10

30

11

11

80

01

11

10

02

11

00

07

10

30

03

10

00

12

10

10

01

10

30

17

10

30

08

10

30

12

11

00

02

10

30

10

10

30

14

11

00

09

11

50

05

11

90

05

Ch

ange

in B

ase

line

(%

) ADXS

ADXS/CIS

N=69 response-evaluable patients

LTS – Long Term Survival

PD – Partial Disease

SD – Stable Disease

PR – Partial Response

CR – Complete Response

PD

PD

PDSD

SDSD SD SD SDSDSD SD SD SD PR PR

CR

CR

CR CR

Additional long-term survivors discontinued prior to tumor evaluation

LTS = alive > 18 months from randomization


• 38% rate of disease control (CR+PR+SD)

• 22% rate of survival >18 months


Attenuated Listeria monocytogenes (Lm) as an Antitumor Vector

• Lm was first demonstrated to be an effective vector for cancer

immunotherapy in 1995 (Yvonne Paterson, PhD, Nature Medicine)

Factors impacting Lm vector efficacy and safety:

Method of attenuationDelete virulence factors for safety but retain necessary characteristics for tumor immunity

Copy Number of Tumor AntigensMulti-copy plasmid for increased antigen expression vs single insertion on chromosome

Constant Secretion of Fusion-PeptideConstitutive secretion of multiple copies of fusion peptide facilitates early intracellular antigen

release, processing and subsequent presentation

Features of the fusion protein partnerThe TAA fusion protein partner should optimally enhance direct antitumor immunity conveying potent

cytotoxic T lymphocyte induction and neutralize tumor protecting cells, without the need for

exogenous immunomodulation (eg, cyclophosphamide, GM-CSF)

Selection of a tumor associated antigen (TAA)Uniquely expressed or overexpressed on tumor

1

2

3

4

5


Platform Versatility

Advaxis has developed several product constructs leveraging the company’s platform technology

Lm-LLO

Dual Antigen Constructs

PSAProstate Cancer

Pre-Clinical

HMW-MAAProstate Cancer

Pre-Clinical

+

+Lm-LLO

HMW-MAABreast CA

Pre-Clinical

+

+

Her2/NeuBreast CA

Pre-Clinical

Lm-LLO+

+

Her2/NeuBreast CA

Pre-Clinical

CA9Breast CA

Pre-Clinical

41

https://www.google.com/url?q=http://en.wikipedia.org/wiki/Prostate-specific_antigen&sa=U&ei=i4xFU8nMCIPb2AX-3IDoAg&ved=0CC4Q9QEwAA&usg=AFQjCNG052HYvRTqn9OkQ4begLIwydOQRw

https://www.google.com/url?q=http://en.wikipedia.org/wiki/Prostate-specific_antigen&sa=U&ei=i4xFU8nMCIPb2AX-3IDoAg&ved=0CC4Q9QEwAA&usg=AFQjCNG052HYvRTqn9OkQ4begLIwydOQRw




Merck Anti-PD-1 (KEYTRUDA / pembrolizumab)

Combination Therapy Collaboration

42

Study Design

• Phase 1/2, open-label, multicenter, 2-part dose-finding, safety and tolerability

study in patients w/ mCRPC w/ a Part B expansion cohort (Total n = ~70)• Part A evaluates ADXS-PSA as monotherapy in patients (n = ~20) with mCRPC

• Part B evaluates ADXS-PSA in combination w/ pembrolizumab (MK-3475) in

patients (n = ~20) w/ mCRPC followed by an expansion cohort (n = ~30)

Scope of Collaboration Agreement

• Advaxis is executing study w/ Merck providing pembrolizumab drug supply

• Joint Development Committee to provide study oversight

• Advaxis is financing study


AZ/MedImmune Anti-PD-L1 (MEDI4736)


43

Study Design

• Phase 1/2, open-label, multicenter, 2-part study evaluating ADXS11-001 and

MEDI4736 administered as monotherapy or in combination in patients (n =

~66) w/ metastatic squamous or non-squamous carcinoma of cervix or

metastatic HPV+ squamous cell carcinoma of head and neck• Part A evaluates combination of ADXS-HPV and MEDI4736 to determine safety and

tolerability of 2-drug immunotherapy regimen (n = ~6-18)

• Part B randomizes patients 1:1:2 to ADXS-HPV:MEDI4736:ADXS-HPV+MEDI4736

(n = ~48)


• Advaxis is executing study w/ AZ/MedImmune providing MEDI4736 drug

supply

• Joint Development Committee to provide study oversight

• Advaxis is financing study


Incyte IDO1 epacadostat (INCB024360)


44

Study Design

• Phase 2, multi-center, open-label preoperative window study

• Evaluate ADXS-HPV as monotherapy and ADXS-HPV in combination w/

epacadostat (INCB024360) in patients (n = ~24) w/ stage I-IIa cervical cancer

• 2 arms, randomized in 1:1 ratio• Arm A: ADXS-HPV as monotherapy (n = ~12)

• Arm B: ADXS-HPV in combination w/ epacadostat (INCB024360) (n = ~12)


• Incyte to submit / hold combination IND and execute study

• Joint Development Committee to be established

• Shared cost (50:50 split)

jefferies 2015 healthcare conference › cmsfiles › jefferies.com › files › advaxis.pdf ·...

Documents