HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY - Leslie Chong Managing Director & CEO
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
HARNESSING
B-CELLS FOR
CANCER
IMMUNOTHERAPY
Leslie Chong
Managing Director & CEO
February-March 2019
HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
N O T I C E : F O R WA R D L O O K I N G S TAT E M E N T S
Any forward looking statements in this presentation have been prepared on the basis of a number of assumptions
which may prove incorrect and the current intentions, plans, expectations and beliefs about future events are subject
to risks, uncertainties and other factors, many of which are outside Imugene Limited’s control. Important factors that
could cause actual results to differ materially from any assumptions or expectations expressed or implied in this
brochure include known and unknown risks. As actual results may differ materially to any assumptions made in this
brochure, you are urged to view any forward looking statements contained in this brochure with caution. This
presentation should not be relied on as a recommendation or forecast by Imugene Limited, and should not be
construed as either an offer to sell or a solicitation of an offer to buy or sell shares in any jurisdiction in which it would
be a contravention of applicable law.
2
HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
EXECUTIVE SUMMARY
01 02 03
Investment Highlights Imugene B-cell Vaccine Pipeline Experienced Management
& Board
• Novel immuno-oncology B-cell • Phase 1 clinical data in Her-2 breast • Meeting milestones
peptide vaccine technology and gastric cancers
• Outstanding scientific provenance • Successful M&A activity
• HER-Vaxx:
from leading U.S. and European • Internationally recognised
Phase 1b recruitment completed
universities Phase 2 activity commenced members of the Scientific
• Drug is safe and well tolerated Advisory Board
• Sound cash position • B-Vaxx:
Phase 2 ongoing
• Robust intellectual property portfolio &
long patent life including checkpoint • KEY-Vaxx:
inhibitor combinations pre-clinical work started
• Manufacturing straightforward with Phase 1 to commence in 2019
low cost of goods
• Published in leading peer review
journals
3
INVESTOR PRESENTATION
A TEAM WITH A TRACK RECORD IN DRUG DEVELOPMENT
Leslie Chong Paul Hopper Dr Axel Hoos Mr Charles Walker
SYDNEY, AU SYDNEY, AU PHILADELPHIA, USA BRISBANE, AU
Managing Director & CEO Executive Chairman Non-Executive Director Non-Executive Director
• Over 20 years of • International & ASX • Senior Vice President • Experienced listed biotech
oncology experience in biotech capital markets and Head of Oncology at CEO and CFO (ASX;ACL
Phase I – III of clinical experience particularly in GSK and ASX:IMU)
program development immuno-oncology & • Former Medical Lead for • Experienced in financial
• Leadership role vaccines Yervoy, the first survival markets including
involvement in two • Former Chairman of improving medicine in executing 55 international
marketed oncology Viralytics, Founder & Immuno-Oncology tech corporate
products Director of Prescient, • Chairman of the BoD of transactions
• Previously Senior Founder of Imugene & • Clinical experience
the Sabin Vaccine
Clinical Program Lead Polynoma LLC, former Institute includes managing pipeline
Director pSivida,
at Genentech, Inc., in • Co-Chair of the Cancer of drugs
Somnomed
San Francisco Immunotherapy in all stages form
& Fibrocell Science discovery, through to
Consortium Think-Tank
DrPhase
Anthony Good
III to launched
Dr Mark Marino Dr Nick Ede SYDNEY, AU
MELBOURNE, AU products
CALIFORNIA, USA Vice President of Clinical
Chief Medical Officer Chief Technology Officer Research
• Over 28 years of experience • Over 25 years peptide • Over 20 years
in drug development vaccine and drug global clinical development
• Former CMO of Cytori, development experience.
Head of Clinical • Former CEO Adistem, • Integral to the development
Pharmacology CEO Mimotopes of significant new
at Eisai and Roche, Head • VP Chemistry Chiron medicines including Viagra,
of Research and Early (now Novartis), Research Revatio, Lipitor, and
Development at Mannkind, Somavert.
Fellow CRC Vaccine
VP Clinical Development
Technology • Ex Pfizer Global Research
at Daiichi
and Development, Ex
Covance Clinical Services.
4
INVESTOR PRESENTATION
IMUGENE SCIENTIFIC ADVISORY BOARD
Prof. Josep
Prof Tanios BekaiI
Tabernero
Prof Pravin Kaumaya Dr. Michael Galigiuri VALL D’HEBRON, BARCELONA, Saab
OHIO STATE UNIVERSITY, USA CITY OF HOPE, USA SPAIN MAYO CLINIC, USA
• Prof of Medicine • President of European
• President of City of Hope • Professor of College of
Department of Obstetric Society for Medical
National Medical Center Medicine and Science
Gynecology at Ohio State Oncology (ESMO)
and holds the Deana and • Program Co-Leader, GI
University
Steve Campbell • President of the Medical Cancer, Mayo Clinic
• Research focus in tumour Physician-in-Chief. Oncology Department at Cancer Center
immunology, mechanisms • Elected President of the the Vall d’Hebron
of tumour cell-immune American Association for • Medical Director, Cancer
• Director of the Vall Clinical Research Office
cell interactions, and Cancer Research (AACR)
d”Hebron Institute of (CCRO)
immune mechanisms in 2017
Oncology (VHIO)
• Research focus on fields • Senior Associate
of vaccine with emphasis Consultant, Mayo Clinic
on peptide vaccines for AZ
cancer
Prof Peter Schmid Prof. Ursula
BARTS CANCER INSTITUTE, Wiedermann-Schmidt Dr Neil Segal Dr Yelina Janjigian
QUEEN MARY UNIVERSITY OF MEDICAL UNIVERSITY OF VIENNA, MEMORIAL SLOAN KETTERING MEMORIAL SLOAN KETTERING
LONDON AUSTRIA CANCER CENTER, USA CANCER CENTER, USA
• Co-inventor of HER- • Medical Oncologist • Medical Oncologist
• Medical Oncologist
Vaxx • Expertise in GI, Colon,
• Expertise in breast and • Expertise in esophageal
• Professor of Pancreatic cancers and stomach (gastric)
lung cancer, cancer
immunotherapy and early Vaccinology at Medical • Active clinical immuno- cancer
drug development University of Vienna oncology researcher • Active in GI clinical trials
• Leads the Centre of • Clinical lead in several testing combinations of
Experimental Medicine at trials using PD-L1 Her-2 and checkpoint
Barts Cancer Institute inhibitors inhibitor therapies
5
HARNESSING B-CELLS FOR CANCER
IMMUNOTHERAPY
Imugene develops
vaccines
to boost and direct the
body’s immune system
to specifically target and
attack cancer cells
6
HARNESSING B-CELLS FOR CANCER
IMMUNOTHERAPY
IS THERE
A BETTER
WAY TO MAKE
Monoclonal antibodies ANTIBODIES Using B-cells
are manufactured in a TO TREAT in your body
facility CANCER? Teaching B-cells to
make antibodies using
For example, Merck’s
peptide antigens
PD-1 inhibitor Keytruda®
B-cells are cells
in the human
body that
naturally
produce millions
of antibodies
7
HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
HER-VAXX MIMOTOPE: MECHANISM OF ACTION?
Peptides “mimic”
the epitope HER-VAXX
ANTIBODY
TUMOR
SECRETION CELL
Via helper T-cells
HER-2/NEU
3
PEPTIDES
HER-VAXX B-CELL
IMMUNOTHERAPY A C T I VAT I O N
Epitope = Antibody
Binding Site
B CELL HER-Vaxx attacks the same target
as the the world’s largest selling
breast cancer drug Herceptin®
8HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
CURRENT PHASE 1B/2, IN GASTRIC CANCER
Phase 1b -
Complete
2H, 2017
PHASE 1B
PATIENTS
ENROLLED
Trial Patients Study Endpoints Study Results
• Phase 1b • Gastric HER-Vaxx in • Recommended • 50 µg selected as the
• Open Cancer combination Phase 2 Dose of RP2D
label • Up to 18 with chemo: HER-Vaxx • No safety or toxicity
patients Cisplatin and • Safety and Toxicity issues 2H, 2018
in 3 cohorts 5FU PHASE 1B
• Immunogenicity • All patients had COMPLETED
(10, 30 and or
(anti-HER-2 increased antibody
50 µg) capecitabine
antibody titres) response
• Best Response Rates
• 1 Complete
Response
• 5 Partial Response
• 4 Stable Response
9HARNESSING B-CELLS FOR CANCER
IMMUNOTHERAPY
CURRENT PHASE 1B/2, IN GASTRIC CANCER
Phase
1H, 2019:
2 COMMENCE
PHASE 2
Trial Patients Study Primary Endpoints
• Phase 2 • Gastric Randomized • OS
• Open label Cancer HER-Vaxx in combination • PFS
• Up to 70 with standard of care TBD:
patients chemotherapy Secondary INTERIM
Or Endpoints PHASE 2
DATA
Standard of care chemo: • Safety and AVAILABLE
Cisplatin and 5FU or Tolerability
capecitabine or oxaliplatin • Immune response
10Three year 11
HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
R&D contract with
access to Ohio
translational labs
Access to
experience and
expertise with
Prof. Pravin
Kaumaya and
team
Six additional
clinical
candidates Her-1,
STRATEGIC Her-2, Her-3,
AQUISITIO VEGF, IGF-1R
Six patent
CD28
N families,
22 patents
Worldwide
IND ready exclusive
PD-1 clinical license
trial (Phase 1) Ongoing Her-2
clinical trial
(Phase 2)HARNESSING B-CELLS FOR CANCER
IMMUNOTHERAPY
COULD PRECISION-
ENGINEERED
PEPTIDE EPITOPES/
VACCINES BE THE
KEY TO A CANCER “Combination cancer vaccines
with peptide mimics have the
CURE? potential to treat existing cancer
and prevent its reoccurrence.”
PROF PRAVIN KAUMAYA
OHIO STATE UNIVERSITY, USA
DR TANIOS BEKAII SAAB
MAYO CLINIC, USA
12HARNESSING B-CELLS FOR CANCER
IMMUNOTHERAPY
ACQUIRED HER-2 VACCINE (B-VAXX)
ENCOURAGING
PHASE 1 TRIAL
R E S U LT S
14
24 Patients had
stable disease
2 out of 24 patients had partial response
1 patient had PFS at 40+ months
NO TOXICITY
OBSERVED
Phase Ib Immunotherapy Trial with a Combination of Two Chimeric (Trastuzumab-like and Pertuzumab-like) HER-2 B Cell Peptide Vaccine emulsified in ISA 720 and nor-MDP Adjuvant in Patients with Advanced Solid Tumors, Immunological Response
and Clinical Outcome. Tanios Bekaii-Saab, Daniel H. Ahn, Christina Wu, Robert Wesolowski, Amir Mortazavi, Maryam Lustberg, Jeffrey Fowler, Bhuvaneswari Ramaswamy, Lai Wei, Jay Overholser and Pravin T.P. Kaumaya. Cancer Discovery 2018
manuscript in preparation.
13HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
IMUGENE PIPELINE
Program Pre-clinical Phase 1 Phase 2
Clinic or
Clinic-ready
HER-Vaxx (HER2)
B-Vaxx (HER2)
KEY-Vaxx (PD-1)
Her-2 & PD-1 Combo
14HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
IMUGENE PIPELINE
Program Pre-clinical ID of candidate
Discovery
Pipeline Her-1 (EGFR)
Her-3
IGF-1R
VEGF
Combination
(numerous)
PD-L1
15HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
WHY SELECT & TARGET PD-1 FOR B-CELL VACCINATION?
Monoclonal antibody
immunotherapies
Keytruda® (Merck) The combination of the
and Opdivo® (BMS) PD-1 vaccine with the
targeting PD-1 sold acquired Phase II Her-2
USD$3.8B and $4.9B, vaccine significantly
respectively, in 2017. inhibits tumor growth
c/w mAb control in a
Her-2+ model of colon Whilst acknowledging the
cancer. rapid rise in clinical trials
involving PD-1 and their
In industry-recognised combination with other
mouse cancer models (colon
cancer), the PD-1 targeting B-cell treatments*, a PD-1 B-cell
vaccine is more superior than the vaccination approach
gold standard mouse PD-1 represents a paradigm shift in
monoclonal antibody (used in
preclinical model testing for cancer immunotherapy.
Keytruda and Opdivo). * Tang etal. Comprehensive analysis of the clinical immuno-oncology 16
landscape, Annals of Oncology, 2017
16HARNESSING B-CELLS FOR CANCER
IMMUNOTHERAPY
PD-1/HER-2 VACCINE COMBINATION
Active in model of colorectal cancer with % Cancer growth inhibition in colorectal cancer
no signs of toxicity model
PD-1 vaccine plus Her-2 vaccine 90%
All mice vaccinated over a period of 9 weeks showed no
signs of scruffiness, lesions, and lethargy.
PD-1 vaccine 65%
Organs (spleen, liver, heart, lung, kidney, and tumor) from
the Balb/c mice vaccinated with combination peptides
(HER-2 and PD-1) were collected from mice and
submitted for analysis. PD-1 mAb 39%
No significant lesions were noted in any of the organs
submitted for histologic evaluation.
Control (PBS) 0%
There were also no overt biochemical abnormalities noted. 0% 23% 45% 68% 90%
Inhibition of cancer growth 16 days after infusion of cancer cells
17HARNESSING B-CELLS FOR CANCER IMMUNOTHERAPY
PD-1 ‘KEY-VAXX’ VACCINE PHASE 1 DEVELOPMENT PATH 2018-2019
PRE-CLINICAL
MILSTONES
PD-1
Finalise 2019:
candidate CMC Formal FDA/IND
regulatory IND Commence
vaccine manufacturing pre-clinical granted
submissions Phase 1
identified
Phase 1 – Dose Seeking /Signal Finding Phase 2 – Expansions Assumption
I N PAT I E N T P H A S E S
PROPOSED
COHORT 3 | 3-6 PATIENTS
IDENTIFY OUTCOMES
Indication Expansion
(12-20 patients)
Optimal ✓ Safety Proof of
COHORT 2 | 3-6 PATIENTS Biological ✓ Immunogenicity Expansions
Dose (OBD) ✓ Tumor PD Concept
Indication Expansion
COHORT 1 | 3-6 PATIENTS (12-20 patients)
18HARNESSING B-CELLS FOR CANCER
IMMUNOTHERAPY
FINANCIAL SUMMARY
Options on issue
NO. OF EXERCISE
EXPIRY Market Cap
OPTIONS PRICE
(Jan 19)
Listed: (IMUOA) 242.5M $0.026 30/11/2020
$64.9M AUD
Listed:(IMUOB) 248.3M $0.04 30/11/2021
$46.5M USD Ordinary shares
Unlisted: 134.5M $0.0247* 09/03/2020*
3.610B
Total: 625.3M $0.03* 02/01/2021*
12 month price range
Top 5 shareholders (as at January 2019) NO. OF SHARES % C A P I TA L
Private Portfolio Management 224,551,412 6.22%
1.3c – 4.0c
AUD Average daily volume
141,246,879 3.91%
Platinum Asset Management
6.4M shares
Dr. Nicholas Smith 100,000,000 2.77% (Oct 18 – Jan 19)
Paul Hopper, Executive Chairman 76,178,722 2.11% Investment to date
Sarah Cameron 60,000,000 1.66% ~$42.5M PUBLIC Cash & Equivalents
* Average
~$5.5M VC
$24.05M
(as at 31 Dec 2018)
19Leslie Chong
Managing Director & CEO
leslie.chong@imugene.co
m
+61 458 040 433You can also read
