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CANCER VACCINES RE-IMAGINED: FROM PARIAH TO DARLING
December 10, 2018
2Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
The information in this report has been obtained from what are believed to be reliable sources and has been verified whenever possible. Nevertheless, we cannot guarantee the information contained herein as to accuracy or completeness. All expressions of opinion are the responsibility of Defined Health, and though current as of the date of this report, are subject to change.
The opinions and information set forth herein are expressed solely for the benefit of the addressee and only for the purpose(s) for which the report was produced. Without the prior written consent of Defined Health, this report may not be relied on in whole or in part for any other purpose or by any other person or entity, provided that this report may be disclosed where disclosure is required by law.
This report may contain information provided by third parties such as Clarivate Analytics, Springer, EvaluatePharma, Datamonitor, Informa Healthcare, IMS Health and others with a proprietary interest in the data provided herein. Please note that you are not permitted to redistribute any such third party information without consent from the originator company.
© Defined Health, 2018
3Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
t Moderators:• Jeffrey M. Bockman, PhD, EVP, Oncology Practice Head, Cello Health BioConsulting (Defined Health)• Serom Lee, PhD, Consultant, Cello Health BioConsulting
t Panelists:• Gregory Lizee, PhD, Associate Professor, Departments of Melanoma Medical Oncology and Immunology, MD Anderson Cancer
Center• Pramod Srivastava, PhD, MD, Professor, Department of Immunology, Eversource Energy Chair in Experimental Oncology, Director,
Center for Immunotherapy of Cancer and Infectious Diseases, Director, Carole and Ray Neag, Comprehensive Cancer Center, UCONN
Cancer Vaccines Re-Imagined: From Pariah to Darling
UCONN
6
7Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Is pleased to present:
8Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Is pleased to present:
30TH Annual Cancer Progress ConferenceMay 7 – 8, 2019
Convene at 32 Old Slip, NYCwww.cancerprogressbyDH.com
REGISTER
9
12
13Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
What Will We Discuss? A Lot of Things!
t We will discuss a bit of history around why vaccines have had struggles, TAA/TSA vaccines, role of immunization platforms, adjuvants, and of course neoantigens.
t We will also discuss cancer vaccines in the broader context of immuno-oncology, including alternative concepts to exogenous vaccination such as in situ vaccination through combinations of IO and Non-IO agents and approaches (including chemotherapy and radiation).
t Also, novel concepts, latest academic research in vaccinology for cancert And finally, clinical development issues (moving earlier, etc.).
14
Cancer Vaccines, Long History of Failures and Learnings
15Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Introduction
16Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
In 2011 Defined Health Led a Workshop on Cancer Vaccines…
17Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
From Defined Health’s Cancer Vaccine Talk 2011: Advanced Stage Vaccines, Nature Reviews, 2005
Nature Rev. Drug Discov. 4, 623–624; 2005
18Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
From Defined Health’s Cancer Vaccine Talk 2011: Advanced Stage Vaccines, Nature Reviews, 2009
Nature Reviews Drug Discovery 8, 685-686 (September 2009)
19
Why Are We Even Discussing Vaccines?
20Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Immuno-Oncology Progress Has Been Dramatic
Opdivo website; N Engl J Med. 2018 Apr 16
NSCLC
– In Selected Cancers, for Selected Patients
21Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
But Such Progress Has Not Been Universal: Advances Even with CPIs While Dramatic in Certain Situations Remain Incremental and/or Limited in Many Others
Cello Health BioConsulting (Defined Health) Analysis: ESMO, ASCO, AACR, ASH abstracts; prescribing information; company press releases; *efficacy data is weighted by the number of patients per trial, total number of patients across all trials and number of trials represented are in y-axis label
0 5 10 15 20 25 30
SCLC, PDL1+/-, 2L (n=98, 1 trial)GC/GEJ, PDL1+/-, 3L (n=589, 2 trials)
Bladder, PDL1+/-, 3L (n=66, 1 trial)GC/GEJ, PDL1-, 3L (n=115, 1 trial)
Bladder, PDL1+/-, 4L (n=41, 1 trial)NSCLC, PDL1-, 2L (n=108, 1 trial)
Bladder, PDL1+, 2L (n=74, 1 trial)GC/GEJ, PDL1+/-, 2L (n=124, 2 trials)
HNC, PDL1+/-, 2L (n=279, 2 trials)Sarcoma, PDL1+/-, 2L (n=38, 1 trial)
Breast TNBC, PDL1+/-, 2L (n=170, 1 trial)SCLC, PDL1+/-, maintenance (n=45, 1 trial)
NSCLC, PDL1-, 3L (n=93, 1 trial)HNC, PDL1+, 2L (n=260, 2 trials)
Bladder, PDL1+/-, neo/adjuvant (n=56, 1 trial)Bladder, PDL1+/-, 2L (n=1337, 6 trials)
Ovarian, PDL1+/-, 2L (n=124, 1 trial)NSCLC, PDL1+/-, 2L (n=996, 4 trials)
Mesothelioma, PDL1+/-, 2L (n=89, 2 trials)HCC, PDL1+/-, 2L (n=39, 1 trial)
Bladder, PDL1+/-, 1L (n=119, 1 trial)NSCLC, PDL1+, 2L (n=1242, 5 trials)
NSCLC, PDL1+, 3L (n=146, 1 trial)NSCLC, PDL1+, 1L (n=49, 1 trial)RCC, PDL1+/-, 2L (n=410, 1 trial)
Months
Aggregated PD1/L1 Efficacy per Tumor Type and Setting: mOS
N Engl J Med 2017; 377:2500-2501
HOTTER TUMORS
COLDER TUMORS
22Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Nature. 2017 Jan 18;541(7637):321-330
Our Conceptual Framework Is Evolving, Our Understanding Is Maturing: The Cancer Immunity Cycle 2.0: Immune Desert, Excluded & Inflamed
23Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
The Goal
Cytokine Growth Factor Rev. 2017 Aug;36:5-15
24
So, Is Anyone Really Developing Cancer Vaccines Anymore?
25Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Cancer Vaccines Remain Abundant in All Phases of Development With Most of the Newer Modalities Are in Earlier Development
Source: Adis R&D Insight, Clarivate Analytics Cortellis; Cello Health BioConsulting (Defined Health) Analysis
0
50
100
150
200
250
300
350
Phase 1 Phase 2 Phase 3 Pre-registered Registered Marketed
Num
ber o
f Age
nts
Phase of Development
US IO Pipeline by Highest WW Phase and Mechanism(n=635)
Viral vaccine and/or oncolytic
Other IO (ADC)
Other Cell Therapy
Innate Immunity (antagonist)
Innate Immunity (agonist)
Immuno-metabolism
Cytokine
Costim
Checkpoint
CAR-T cells
Cancer vaccine
Bispecific (IO Redirecting)
* Undefined Mechanism included in Other IO (ADC); Bispecific (IO Redirecting) includes IO/IO targeting Bispecifics
26Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
The Clinical Activity, as Reflected in Latest CRI Analysis, Shows Astonishing Increases in the Past Year Alone, Especially for T-Cell Targets/MOAs & Cell Therapies
Nat Rev Drug Discovery 2018 Oct 19, courtesy of CRI
27Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
US IO Pipeline Heat Maps (Count) – Selected Solid Tumors
Source: Adis R&D Insight, Thomson Reuters Cortellis; Cello Health BioConsulting (Defined Health) Analysis
Highest Count Key
1 20 50
Count of Agents in Development per Mechanism by Indication P1->MRKT Ca
ncer
Solid
tum
or
GBM
/Glio
ma
Head
and
nec
k ca
ncer
Thyr
oid
canc
er
Brea
st c
ance
r
Ova
rian
canc
er
Pros
tate
can
cer
RCC/
Rena
l can
cer
Blad
der c
ance
r
Colo
rect
al c
ance
r
NSC
LC
Smal
l cel
l lun
g ca
ncer
Lung
can
cer
Mel
anom
a
Panc
reat
ic ca
ncer
HCC/
Live
r can
cer
Esop
hage
al c
ance
r
Gas
tric
can
cer
Gas
troi
ntes
tinal
can
cer
Sarc
oma
Carc
inom
a
Canc
er m
etas
tase
s
Bispecific (IO Redirecting) 1 6 1 1 1 1 1 1 1
Cancer vaccine 25 19 22 7 1 42 24 29 8 6 12 18 3 7 34 8 4 4 3 3 2
CAR-T cells 9 3 9 1 3 2 1 3 3 1
Checkpoint 9 36 7 9 3 6 7 6 9 4 8 10 8 2 9 6 7 6 8 1 2 4
Costim 4 18 2 3 1 2 2 1 1 4 1 1 1
Cytokine 8 12 2 2 7 2 5 3 4 4 3 15 5 1 1
Immuno-metabolism 3 8 3 1 2 1 1 1 5 1 2 1
Innate Immunity (agonist) 3 7 1 3 3 3 2 5 2 1 5 3 1 1Innate Immunity (antagonist) 5 14 1 1 2 1 1 1 1 1
Other cell therapy 4 10 4 8 1 2 2 1 2 1 8 2 2 1 1 3
Other IO (ADC) 2 1 1Viral vaccine and/or oncolytic 7 14 10 10 1 6 11 9 2 3 10 5 1 3 10 6 6 2 3 2 2
*Bispecific (IO Redirecting) includes IO/IO Targeting Bispecifics
28Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Majority of Cancer Vaccines Are Targeting TAAs, While About 20% Are Targeting Neoantigens
135
118
46
34
2910 10 8
Count of Cancer Vaccine Agents by Modality (n=393)
Peptide
DC
Whole tumor cell
Viral vaccine
DNA
Bacteria
RNA
Undefined
Nanoparticle
Parasite
Yeast
Source: Adis R&D Insight, Clarivate Cortellis
225
64
26
24
2119 11 3
Count of Cancer Vaccine Agents by Target Type (n=393)
TAA
Personalized (WholeTumor/Lysate)Undefined
Neoantigen
Viral
Allogenic whole tumor
Allogenic Tumor Lysate
Shared Neoantigen
Viral/TAA
11
29Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Re-Energized Vaccine Pipeline Pins Hope on Improvements in: Growing Spectrum of Immunization Platforms
Immunization Platform Spectrum
Proteins/Peptides:
• Short peptides • Synthetic Long Peptides
DNA/RNA• mRNA• Vectors:
• Viral (including oncolytic viruses)
• Bacterial• Yeast• Plasmid DNA
Cells:
• Dendritic cells:• Allogeneic
Autologous • Tumor cells:
• Lysates
30Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Re-Energized Vaccine Pipeline Pins Hope on Improvements in: Growing Spectrum of Immunization Platforms
NUS Medicine
31Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Re-Energized Vaccine Pipeline Pins Hope on Improvements in: Combination Partners Such as Checkpoint Inhibitors
Front Immunol. 2018; 9: 610
32
And What Is All This Neoantigen Stuff About Anyway?
33Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Transforming Cancer Vaccines into Personalized Medicine
Sahin et al., Science 359, 1355–1360 (2018) 23 March 2018
34
Okay, so the Pipeline Is Active, But What About Deals?
35Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
36
Panelist Discussion
37
Novel Concepts in Platforms, Targets, Adjuvants & Other Immunostimulants or Inducers of Immunogenic Cell Death
38Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Various Novel Approaches to Adjuvants, Immunogenic Cell Death, Platforms, and Vaccine Targets
39
The End, & Thank You for Your Time & Attention
40Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
41Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Is pleased to present:
42Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Is pleased to present:
30TH Annual Cancer Progress ConferenceMay 7 – 8, 2019
Convene at 32 Old Slip, NYCwww.cancerprogressbyDH.com
REGISTER
43
Cello Health BioConsulting (Previously Defined Health)
44Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Cello Health BioConsulting (Previously Defined Health)
Leading business development strategy consulting firm, assisting clients in the pharmaceutical, biotech and healthcare investment industries for more than 25 years
Three core lines of business, each focused on helping companies build and strengthen development-stage assets: compounds, portfolios and platforms
45Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Defined Health is a Part of Cello HealthA worldwide team of more than 400 based in the US and UK
A UNIQUE FUSION OF EXPERTISE TO SOLVE PROBLEMS, REDUCE RISK AND UNLOCK THE FULL POTENTIAL OF ORGANIZATIONS, ASSETS AND BRANDS
London
Farnham
Chicago
San Francisco
Philadelphia
New York & New Jersey
Boston
Offices in London, Farnham, New York, San Francisco, Chicago, Philadelphia and Boston
INSIGHT & ANALYTICS
STRATEGY & COMMERCIAL
SCIENCE & EVIDENCE
Market Researchers, Master Practitioners,Digital Specialists, Innovation leads, Field and Compliance
70+ Consultants with a blend of industry experts and consulting specialists
200Communication Specialists, Scientists & Creatives including Client Service, Project Managers and Medical Writers
60+
140
PhDs and MDs providing a depth of understanding into cutting edge science
46Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Defined Health Areas of Expertise and CapabilitiesCore Services
Opportunity Assessments
Portfolio and Platform Strategy
Opportunity Search & Evaluation
47Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Defined Health Core Services
• Assess commercial value in markets of interest
• Evaluate mechanistic approach and scientific rationale
• Position and differentiation from evolving SoC
• Define target patient populations, clinical endpoints and target product profiles
• Determine payer perspective
§ Establish criteria for identifying programs that fit with strategy
§ Identify assets and/or companies that best match criteria
§ Work with our client to prioritize opportunities
§ Provide deeper analysis of priority targets
§ Identify value inflection points to optimize partnering strategy
Opportunity Assessments
Opportunity Search & Evaluation
§ Analyze and prioritize pipeline portfolio
§ Identify and assess novel indications for development
§ Prioritize and sequence potential indications
§ Define value inflection strategy for clinical candidates
§ Advise on optimal time and stage of development for partnering
Portfolio and Platform Strategy
48Cancer Vaccines Webinar, Dec 10© Cello Health BioConsulting 2018
Defined HealthInsight Across the Clinical Development Value Chain, with Particular Focus on Early-Stage Assets
Defined Health’s combination of scientific sophistication and strategic/commercial insight provides a competitive advantage for its core offerings across the clinical development value chain, with particular emphasis on assets in early phases of development.
Preclinical Clinical Launch
Opportunity Assessments, Indication Prioritization, and Strategy
Identify Value Inflection Points, Forecasting and Valuation
Payer Research, Pricing Analysis and Optimization
Opportunity Search and Evaluation
Scientific Focus: Translation of mechanism to potential clinical value proposition
Clinical and Commercial Experience:Guidance on strategies for differentiation