CANCER VACCINES RE-IMAGINED: FROM PARIAH …...tWe will discuss a bit of history around why vaccines have had struggles, TAA/TSA vaccines, role of immunization platforms, adjuvants,

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


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


Is pleased to present:



30TH Annual Cancer Progress ConferenceMay 7 – 8, 2019

Convene at 32 Old Slip, NYCwww.cancerprogressbyDH.com

REGISTER

https://www.cancerprogressbydh.com/

9

12


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.).

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Cancer Vaccines, Long History of Failures and Learnings


Introduction


In 2011 Defined Health Led a Workshop on Cancer Vaccines…


From Defined Health’s Cancer Vaccine Talk 2011: Advanced Stage Vaccines, Nature Reviews, 2005

Nature Rev. Drug Discov. 4, 623–624; 2005


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?


Immuno-Oncology Progress Has Been Dramatic

Opdivo website; N Engl J Med. 2018 Apr 16

NSCLC

– In Selected Cancers, for Selected Patients

https://www.ncbi.nlm.nih.gov/pubmed/29658856


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


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


The Goal

Cytokine Growth Factor Rev. 2017 Aug;36:5-15

https://www.ncbi.nlm.nih.gov/pubmed/28693973

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So, Is Anyone Really Developing Cancer Vaccines Anymore?


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


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


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


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

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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


Re-Energized Vaccine Pipeline Pins Hope on Improvements in: Growing Spectrum of Immunization Platforms

NUS Medicine


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?


Transforming Cancer Vaccines into Personalized Medicine

Sahin et al., Science 359, 1355–1360 (2018) 23 March 2018


Transforming Cancer Vaccines into Personalized Medicine

Sahin et al., Science 359, 1355–1360 (2018) 23 March 2018

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Okay, so the Pipeline Is Active, But What About Deals?


Selected Big Vaccine Deals Over Past Few Years







40

Panelist Discussion

41

Novel Concepts in Platforms, Targets, Adjuvants & Other Immunostimulants or Inducers of Immunogenic Cell Death


Various Novel Approaches to Adjuvants, Immunogenic Cell Death, Platforms, and Vaccine Targets













49

The End, & Thank You for Your Time & Attention






30TH Annual Cancer Progress ConferenceMay 7 – 8, 2019

Convene at 32 Old Slip, NYCwww.cancerprogressbyDH.com

REGISTER

https://www.cancerprogressbydh.com/

53

Cello Health BioConsulting (Previously Defined Health)


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


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

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INSIGHT & ANALYTICS

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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


Defined Health Areas of Expertise and CapabilitiesCore Services

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Defined Health Core Services

• Assess commercial value in markets of interest

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• Position and differentiation from evolving SoC

• Define target patient populations, clinical endpoints and target product profiles

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§ Establish criteria for identifying programs that fit with strategy

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§ Work with our client to prioritize opportunities

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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


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

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Opportunity Search and Evaluation

Scientific Focus: Translation of mechanism to potential clinical value proposition

Clinical and Commercial Experience:Guidance on strategies for differentiation

Documents

CANCER VACCINES RE-IMAGINED: FROM PARIAH …...tWe will discuss a bit of history around why vaccines have had struggles, TAA/TSA vaccines, role of immunization platforms, adjuvants,