IDEAYA Biosciences

JP Morgan Healthcare Conference

January 10, 2018
IDEAYA Biosciences – Corporate Overview
Building the Next Generation Oncology Company
Innovation Focus Organization
Novel Small Molecules Proven Leadership
Synthetic Lethality & IO World-Class Science

Applying Synthetic Lethality for the

Selective Targeting of Cancer

Mutational landscape determines sensitivity

to PD-1 blockade in non-small cell lung cancer

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IDEAYA: Blue Chip and Top Oncology Strategic Investors

$46M Series A – March 2016

COVER STORY

COVER STORY

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Building the Premier Oncology Pipeline
Synthetic Lethality and Immuno-Oncology

Personalized Medicine Immuno-Oncology

Biomarker enabled Small Molecule focus
• SL PoC: BRCA screening • Strategic differentiation vs. ABs
doubles PARP clinical response
SYNTHETIC IMMUNO- and cell-based therapies
• Unexploited SL interactions LETHALITY ONCOLOGY • Core focus areas
beyond PARP-BRCA o Immuno-Metabolism
• Time is now: CRISPR, Cancer o Innate Immunity
Genome Atlas, Sequencing

DNA Damage + IO
DDR & Neoantigens
IO + SL Clinical Combos
“Cold” to “Hot” Tumors

SL = Synthetic Lethality
PoC = Proof of Concept
DDR = DNA Damage Response, DNA Damage Repair
IO = Immuno-Oncology
AB = Antibodies
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IDEAYA Leadership Team
Extensive Experience Building Top Oncology Companies

Leadership Team
• Yujiro S. Hata, M.B.A., Co-Founder and CEO
– 20-years experience building private and public biotech companies
– COO, Flexus and spinout FLX. Acquired by BMS for $1.25 billion
– VP, Head M&A and Licensing, Head Strategy and SAM, Onyx. Acquired by Amgen for $10B
– VP, SVP, and CBO, Enanta (NASDAQ: ENTA).
– Board of Directors at Xencor (NASDAQ: XNCR), Expansion Therapeutics & UCSD Cancer Center; EIR, 5AM Ventures

• Jeff Hager, Ph.D., Co-Founder, SVP, Head of Biology

– 20-years experience in tumor biology, cancer pharmacology, and oncology drug discovery
– Vice President, Head of Biology, Seragon. Acquired by Genentech $1.7B
– Senior Director, Director, Head of Biology, Aragon. Acquired by JnJ for $1B
– Associate Director, Apoptos; Principal Scientist, Kalypsys; UCSF, Staff Scientist

• Michael P. Dillon, Ph.D., F.R.S.C., SVP, Head of Drug Discovery

– 20-years of small molecule drug discovery experience in large pharma
– Global Head, Oncology and New Therapeutic Modalities Chemistry, NIBR, Cambridge
– Executive Director, Oncology Chemistry and Head of Chemical Sciences, NIBR, Emeryville
– Director, Medicinal Chemistry, Roche, Palo Alto

• Tim Smith, M.B.A., M.A., SVP, Head of Corporate Development

– 15-years experience in capital markets, investor relations, and business development
– CBO, Cleave Biosciences
– Executive Director, Business Development, Director, Investor Relations, Celgene
– Senior Director, Investor Relations, MGI Pharma; Associate, Biotechnology Equity Research, Citi

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 IDEAYA Organization
Our Value = Our People, 39 FTEs and growing
San Francisco Yujiro Hata
CEO
San Diego Flexus (BMS), Onyx
(Amgen), Enanta (IPO)

Jeffrey Hager, Ph.D.

Michael Dillon, Ph.D. Tim Smith
SVP, Biology
19 Seragon (Genentech),
15 SVP, Drug Discovery 4 SVP, Head of Corp Dev
Cleave, Celgene
Novartis, Roche
Aragon (JnJ)

Jim Joseph, Ph.D. Eleni Venetsanakos, Ph.D. Hilary Beck, Ph.D. Jim Sutton, Ph.D. Zhonghua Pei, Ph.D. Claire Neilan, Ph.D. Andres Briseno, CPA
Lisa Belmont, Ph.D. Fred Aswad, Ph.D.
Assoc. Director, Dir, Pharm. Dir, MedChem Sr. Dir, MedChem Dir, MedChem Dir, PreClin Sciences Controller
Director, SL Biology Sr. Dir, IO Bio
Discovery Biology Principia, 8-yrs Novartis, Flexus, 12-yrs Novartis, 10-yrs Genentech, 2 yrs Gilead, AbbVie/Pharmacyclics,
10-yrs Genentech 9-yrs Bayer 5-yrs Chiron
Seragon, Aragon 9-yrs Amgen 8-yrs BMS 10-yrs Abbot 9-yrs Incyte Theravance, PwC

Marcos Gonzalez- Jerome Ort

Lorn Kategaya, Christian Frey, Ruben Martinez, Richard Steel,
Jing Lu, Ph.D. Kedar Vaidya Lopez, Ph.D. Accounting

IDEAYA R&D Experience

Ph.D., SRS Ph.D. Ph.D., SRS, Ph.D., SRS,
Principal Scientist PRS, Pharmacology MedChem Principal, MedChem Manager
5-Yrs Genentech, Principal Scientist
Arvinas, Novartis 8-yrs AbbVie MedChem Theravance,
UCSF 9-yrs Gilead Scripps, UC Irvine Scripps
Ignyta, Scripps Deloitte

Brian Jones, Ph.D., Melissa Fleury Jennifer Hu

Leenus Martin, Tzuling Cheng, Candy Garcia Marcus Fisher Muzaffar Alam
Ph.D., SRS Ph.D., SRS SRS, MedChem SRS, MedChem Sr. Admin/
RS, IO Bio RS, Pharmacology RS, MedChem
+50 years at
Ignyta, NYU Pelaton, UTSW 16-yrs BMS 10-yrs Oncomed
Scripps,
+40 years at
Northwestern
17-yrs Roche
Reset, MyoKardia,
10 yrs Theravance
Office Manager
Facebook

Aurora Martinez-
Christina Galang Nandini Alice Rico Alexander Bayden,
Hadia Lemar Horta Leah Cleary, Ph.D.
Research Scientist Ravindran RS, MedChem Ph.D.
RS, IO Bio SRA, Pharm SRS, MedChem CompChem, SRS
20-yrs Novartis/ SRA 16-yrs Chiron/
16-yrs BMS (12/2017) Pfizer, Caltech
GNF Northwestern Novartis CMD, Astra-Zeneca
UC Davis
Bing Yao
Senthil Perumal, RS, Anal Chem
Ph.D., SRS and Bioanalysis
+40 years at Genapsys, PSU
+30 years at Cleave,
Cytokinetics

Jason Drummond
Research Scientist
16-yrs Genentech
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IDEAYA Board of Directors
Broad Operating and Investment Experience

Board of Directors
• John Diekman, Ph.D., Chairman
– Founding Partner, 5AM Ventures
– Chairman, Scripps; Board Trustee, Princeton

• Tim Shannon, M.D.

– General Partner, Canaan
– Board of Director, Cytomx and Novira (JnJ)

• Terry Rosen, Ph.D.

– CEO, Arcus Biosciences
– CEO, Flexus Biosciences (BMS)

• Brian Daniels, M.D.

– SVP Head of Clinical, BMS
– Board of Director, Novo Nordisk

• Jeff Stein, Ph.D.

– CEO, Cidara Therapeutics (NASDAQ)
– CEO, Trius Therapeutics (Cubist/Merck)

• Yujiro S. Hata, M.B.A.

– CEO, IDEAYA Biosciences

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IDEAYA Scientific Advisory Board
World-Class Science

DNA Damage and Synthetic Lethality Immuno-Oncology and Drug Discovery

• Alan D’Andrea, M.D. • Lawrence Fong, M.D.

– Director, Center DNA Damage and Repair – Co-Director, Cancer Immunotherapy
– Member, National Academy of Medicine – Co-Clinical Director, Parker Foundation

• John Petrini, Ph.D. • William Sellers, M.D.

– Paul A. Marks Chair, Molecular Cell Biology; – Core Institute Member; Former Global Head
Director and Founder of Oncology Research, Novartis

• Trey Ideker, Ph.D. • Paul Reider, Ph.D.

– Division Chief, Medical Genetics, Director, – Lecturer and Professor, Chemistry
National Resource for Network Biology – Former VP Chemistry at Merck and Amgen

• Stephen Kowalczykowski, Ph.D. • Laura Shawver, Ph.D.

– Dir, Center for Genetics and Development – CEO, Cleave Biosciences
– Member, National Academy of Sciences – Former President, Sugen (acquired by Pfizer)

• Elizabeth Swisher, M.D.

– Director, Breast and Ovarian Cancer
Prevention Program

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IDEAYA is Pioneering the Next Generation of Biomarker
Enabled Synthetic Lethality Therapies
Today Next Generation IDEAYA SL Pipeline

PARG DDR2
BER (XRCC1), HRD (15% Colorectal)
PARP (16% Breast, 40% Gastric)
HRD (BRCA)
(15% Ovarian)
Olaparib (Astra-Zeneca)
Niraparib (Tesaro) DDR3 Dual CRISPR
Rucaparib (Clovis) (15% Ovarian) SL Platform

HRD = Homologous Recombination Deficiency

BER = Base Excision Repair

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 Poly (ADP-ribose) Glycohydrolase (PARG)

Biology: PARG Biology

• PARP uses NAD+ to make poly(ADP-ribose)
(“PAR”) at sites of DNA damage
• PAR recruits proteins required for
DNA Repair
• PARG cleaves PAR chains, completing
cycle for DNA repair
PAR Chains
Degraded by
PARG
In response to DNA damage PARGi leads to:
• DNA Double Strand Breaks (DSB)
• Accumulation of PAR chains depletes NAD+
building blocks
• NAD+ depletion causes ATP depletion which leads to cancer cell death

Mechanistic differences between PARP and PARG inhibition:

• PARP inhibition impairs single strand break repair leading to DSB in context BRCA deficiency
• PARG inhibition leads to cancer cell death through DSB accumulation and
NAD+ depletion

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 PARG-XRCC1 Synthetic Lethal Relationship
Survey of Isogenic Cell Lines Reveals XRCC1 Depletion Sensitizes Cells to PARG Inhibition

HeLa Isogenic KD Cell Lines H e L a C C HeLa (Cervical)

C e lls 4 d a y C e ll T ite r G lo

1 5 0
XRCC1 deficientK D

Cell Viability (% Control)

H e L a Is o g e n ic K D c e ll lin e s P A R G i X R C C 1

C o n tr o l)
Control (XRCC1+)
P A R G i C o n tr o l s iR N A

C e ll V ia b ility
1 0 1 0 0
(µ M )

o f D M S O
5 0

5
IC

5 0

(%
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-9 -8 -7 -6 -5
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P A R G i ( lo g M )
C

MCF-7 (Breast) SW620 (CRC)

1 5 0 1 5 0
C o n tr o l s iR N A
C o n tr o l s iR N A

X R C C 1 s iR N A
(% )

(% )
X R C C 1 s iR N A
1 0 0 1 0 0
V ia b ility

V ia b ility
5 0
C e ll

5 0
C e ll

0
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-8 -7 -6 -5 -4
-9 -8 -7 -6 -5 -4

P A R G In h ib ito r (L o g M ) P A R G In h ib ito r (L o g M )

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 XRCC1 Protein Levels Negative/Low in 16% of Breast & 40% Gastric
Potential Target Patient Populations for PARG Inhibitors

IHC Scoring for XRCC1 Protein Levels in Breast Cancer Patient Samples*

(5%) (11%) (32%) (52%)

Breast
• XRCC1 IHC; 1297 patient sample 16% XRCC1 negative/low (H-score ≤100)*
– H-score ≤100 is associated with poor clinical prognosis
Gastric
• ~40% of gastric cancer patients tested (n=612) XRCC1 negative/low (IHC)**
– Wang et al focused on Chinese population; gastric cancer is of high prevalence
Others
• Surveying XRCC1 expression across major cancers and corresponding PDX models (IHC/TMA’s)
– Investigating XRCC1 negative/low by IHC in Prostate, Lung, among others

*Sultana et al Clin Can Res. 2013

**Wang Clin Cancer Res; 18(10) May 15, 2012; Wang Chin J Cancer Res 2016;28(3):355-361
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 PARG Drug Discovery Overview

• IDEAYA advancing PARG program in collaboration with Cancer Research UK

– Strong CRUK DDR legacy from PARP-BRCA
• Two proprietary series of PARG inhibitors have been identified
– National patent filings underway targeting broad international coverage

• Deep SAR understanding and historical knowledge transferred from CRUK

• Amenable to SBDD based on multiple X-ray crystal structures
• SAR on current templates has been expanded and novel templates identified
• Chemistry optimization ongoing towards Development Candidate selection

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 PARG Program Overview
1st-in-Class Program

• Biomarker enabled approach differentiated from PARP with significant

addressable populations
• In vivo PK/PD shows PAR accumulation with 1st generation PARG inhibitor
• Tolerability and MTD studies completed
• IDEAYA PARG inhibitors have improved potency and pharmacokinetics over 1st
generation CRUK molecules
– Cellular potency increased 5 to 100 fold
– Superior exposure profiles: coverage over cellular EC50’s for >24 hours
• Advancing next generation compounds with enhanced potency and PK
• Multigram synthesis ongoing for candidate selection profiling
• Development Candidate selection: Q1 2018
• IND/Phase 1 start: Q1 2019

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 Immuno-Metabolism Program
AhR is Receptor for IDO and TDO Generated Kynurenine

• Aryl-hydrocarbon Receptor (AhR)

is the receptor for IDO and TDO
generated Kynurenine
• In vitro agonists:
– Suppress CD4+ proliferation
– Promote Th17 differentiation
– Promote Treg differentiation
– Promote tolerogenic DC and
B-cell responses
• Promotes immunosuppressive
Nature 478, 192–194 (13 October 2011)
TME through multiple mechanisms
• Other endogenous AhR agonists also have potential to be
immunosuppressive

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 AhR Strategic Positioning vs. IDO
Opportunity to Expand Clinical Indications

IDO+ IDO/ TDO+

Tumors TDO+ Tumors

Targetable by IDO inhibitors Targetable by TDO inhibitors

Targetable by AhR inhibitors

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 Selective IDO Inhibitors Result in Variable Kynurenine
Reduction in Cancer Patients, Pointing to A Clinical Need

50% reduction in Kynurenine

levels with Incyte IDO inhibitor

• Similar Pharmacodynamics observed with BMS-986205 (SITC 2017)

• 50% mean reduction of Kynurenine levels
Hypothesis:
• Variability of Kynurenine inhibition observed with selective IDO inhibition in the clinic
potentially driven by heterogeneity of IDO & TDO expression
• Potential for better therapeutic response with more complete suppression of Kynurenine
signaling via AhR antagonism

17 Epacadostat Phase I Beatty et al,. ClinCanRes 2017

 IDB AhRi Decreases Tumor Associated and M2 Macrophages

CT26-e395 In Vivo Model

TAMs M2 Macrophages
T A M s M 2 M a c r o p h a g e s

4 2 . 5

L e u k o c y t e s
L e u k o c y t e s

2 . 0

1 . 5
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• IDB AhRi monotherapy results in reduction in tumor associated macrophages and tumor
M2 macrophages
• Significant single agent tumor growth inhibition observed in vivo (comparable to IDO +
PD1 combination)

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 AhR Program Overview
1st-in-Class Program

• Superior approach to modulating Kynurenine pathway vs. IDO

• AhR antagonist monotherapy decreases tumor associated & M2 macrophages
• 1st generation AhR antagonist shows superior in vivo efficacy to IDO inhibitor;
trend to enhanced efficacy with PD-1/PDL-1
• Robust single agent activity observed for AhR antagonist, comparable to PD1 +
Incyte IDO inhibitor
• Tolerability & multi-day PK-PD study completed
• Additional potential candidate molecules being synthesized on multigram scale
for candidate selection profiling
• Development Candidate Selection: Q1 2018
• IND/Phase 1 start: Q4 2018

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 IDEAYA Portfolio
Building Industry-Leading Oncology Pipeline

Target Hits and Lead Lead

Program IND/Ph1
Discovery Series ID Optimization
PARG
(XRCC1, HRD)
Q1 2019
DDR2
SYNTHETIC
LETHALITY

(Colorectal)
R&D Engine
DDR3 Goal of 1 IND
(Ovarian, Breast)
per 1-2 years
Dual CRISPR Platform

AhR
ONCOLOGY
IMMUNO-

(Immuno-Metabolism)
Q4 2018

Innate Immunity

Development Candidate nomination (IND-enabling) in Q1 2018 for PARG & AhR

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 2018 – A Pivotal Year for IDEAYA

Significant Research and Corporate Milestones

• Development Candidate Nomination for AhR & PARG in Q1 2018

• IND / Phase 1 for two programs: AhR & PARG

• Advance 3rd program to Development Candidate by year-end

• Series B - Crossover financing in preparation for future IPO

• Establish IDEAYA as the industry leading Synthetic Lethality company

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