Ikena Oncology : Corporate Presentation - Fall 2023

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Corporate Presentation

Fall 2023

Developing Biology-Driven Medicines and Expanding the Impact of Targeted Oncology

We develop differentiated therapies for patients in need that target nodes of cancer growth, spread, and therapeutic resistance in the Hippo and RAS onco- signaling networks

Hippo Pathway

RAS Pathway

• Multiple ongoing clinical trials with expected data readouts in the next 12 months
• Leaders in Hippo pathway with clinical stage TEAD1 inhibitor IK-930
• • Initial monotherapy dose escalation data in all comers, mesothelioma, and EHE in 4Q 2023
  • Broad combination potential including in EGFRm and RASm cancers, starting with osimertinib in NSCLC
• Novel MEK/RAF inhibitor IK-595in IND-enablingstudies
• • IND in 2H 2023 with broad potential across RAF and RAS mutant cancers
• BMS partnered program IK-175with clinical activity in bladder cancer
• • Potential for $50M in opt-infees by early 2024, $450M in milestones plus global royalties
• Cash runway into 2026 with ~$80M added to balance sheet in 2023

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Seasoned Executive Team with 50+ INDs and 14 Regulatory Approvals

23

average years of experience

50+

INDs

14

regulatory approvals

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Executive Team

Mark Manfredi, Ph.D.	Sergio Santillana, M.D.	Jeffrey Ecsedy, Ph.D.	Michelle Zhang, Ph.D.	Jotin Marango,M.D.,Ph.D.
Chief Executive Officer	Chief Medical Officer	Chief Development Officer	Chief Scientific Officer	Chief Financial Officer and
				Head of Corporate Development

				Board of Directors
Owen Hughes	Iain Dukes,	David Bonita,	Jean Francois Formela,	Otello Stampacchia,	Maria Koehler,	Richard Wooster,
Chair	D.Phil.	M.D.		M.D.		Ph.D.	M.D., Ph.D.	Ph.D.

		Scientific Advisory Board
George Demetri, M.D.	Kevan Shokat, Ph.D	Josep Tabernero, M.D., Ph.D.	Neal Rosen, M.D., Ph.D.
Professor, Medicine,	Professor and Chair,	Head of Medical Oncology,	Director, Center for Mechanism-
Harvard Medical School	Department of Cellular and	Vall d'Hebron University Hospital	Based Therapeutics and Chair,
Director, Center for	Molecular Pharmacology, UCSF			Medical Oncology, Memorial
				Sloan-Kettering Cancer Center
Sarcoma and Bone Oncology,	Investigator, Howard Hughes
Dana-Farber Cancer Institute	Medical Institute

Confidential

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Ikena Wholly-Owned Pipeline Focused on Targeted Oncology

Targeted Oncology

Immune-Signaling

Hippo

Pathway

RAS

Pathway

AHR

Signaling

Candidate

Target

IK-930

TEAD

Undisclosed

IK-595

MEK-RAF

Undisclosed

IK-175

AHR

Indications	Partnerships
Interventions	& Rights

Hippo-Altered Cancers

Monotherapy & Multiple

Combinations

Hippo-Altered Cancers

RAS and RAF Altered

Cancers; Additional Tumor

Types

RAS-Mutated Cancers

Bladder Cancer, AHR

Enriched

Monotherapy & Nivolumab

Combination

Head & Neck Cancer, AHR

Enriched

Nivolumab Combination

Discovery	IND Enabling	Phase 1	Late-Stage
Development

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Confidential

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Connectivity Across RAS & Hippo Oncosignaling Network

Nodes in the RAS network are intricately connected to each other and

other orthogonal pathways, including Hippo

Hippo Pathway		RAS Pathway	RAS
NF2		OFF
			GDP
	GRB2
MST1/2
	SOS		RAS
	SHP2	ON	GTP

THERAPEUTIC

LATS1/2

RESISTANCE

13K

RAFPI3K

YAP1/TAZ

MEK

1/2AKT

YAP1/TAZ

ERK1/2mTOR

TEAD

Hippo genetically-altered cancers and Hippo activated resistance

Ikena has deep institutional

knowledge and broad capabilities that lay the foundation for discovery programs across the network

Deep knowledge and characterization

of the interconnected nature of

oncogenic nodes

Proven history of drugging

difficult targets

Leaders in drugging the

Hippo pathway

Advanced capabilities across biomolecular characterization, structural biology, chemistry, and translational medicine

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RASm cancers - one of the most common pathway with genetic alteration in cancers

- potential benefit from monotherapies and combination therapies

Confidential

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Targeting TEAD & the Hippo Pathway

IK-930

IK-930Well-Positioned to Address Diverse Patient Populations with High Unmet Need

Two distinct mechanisms: Genetic alterations in Hippo pathway and pathway involvement in therapeutic resistance

	Hippo Pathway Activity Triggers TEAD		IK-930 Initial Target Patient Populations
	Transcription-Dependent Tumor Growth		Monotherapy
							EHE (0.4 K)
						Combination Therapy
							NF2-def.
	NF2	THERAPEUTIC		Incidence,(AnnualOpportunityU.S.)		Mesothelioma	NF2-def. Malignant
ALTERATIONSGENETIC			(1.2 K)	Meningioma (0.1 K)
	RESISTANCE
	MST1/2	KRAS				Other NF2
	BRAF			Deficient
		CDK
				TKI-resistant
				4/6		Solid Tumors
					EGFRm NSCLC
	LATS1/2	MEK	EGFR			(27 K)	(12 - 16 K)
			ALK
	YAP1/TAZ						EGFRm	Combinations in
							RASm cancers
					IK-930		NSCLC (1L)
	YAP1/TAZ	TEAD DEPENDENT			(20 K)	(multiple populations
		Growing
		TRANSCRIPTION	TUMOR GROWTH			and targets)
	TEAD1	TEAD2 TEAD3 TEAD4
7 EHE: Epithelioid Hemangioendothelioma; MPM: Malignant Pleural Mesothelioma.		Additional potential opportunities in YAP/TAZ amplified cancers
	and combinations with RAS pathway agents (MEKi, KRASi)	7
								Confidential

IK-930 is Potentially both First and Best in Class Targeting Hippo Pathway

IK-930 is a potent Hippo-pathway inhibitor that selectively inhibits TEAD1 and

broadly represses oncogenic TEAD activity

IK-930 is a TEAD1 Selective

Palmitoylation Inhibitor

IK-930

	TEAD1	TEAD2	TEAD3	TEAD4
FP (IC50 μM)	0.88 ± 0.22	9.23 ± 1.80	> 50	6.58 ±
0.93
Click/Chem(IC5	0.2-0.5	>20	>20	>20
0 μM)
TSA (Kd; μM)	0.32	2.47	/	17.85
Nanobret (IC50	0.091 ± .002	15.53 ±	> 20	> 20
μM)	1.32

Pan-TEADi

	TEAD1	TEAD2	TEAD3	TEAD4
FP (IC50 μM)	0.92 ± 0.25	2.29 ± 0.51	1.18 ±	1.38 ±
0.52	0.58
Click/Chem(IC50	0.2-0.5	2	0.5	2
μM)
TSA (Kd; μM)	0.18	1.77	42.82	0.19
Nanobret (IC50	0.030 ± .004 0.51 ± .022	0.041 ±	0.32 ±
μM)	.001	.081

Potent Inhibition of TEAD

	100
Inhibition	80
40
	60
%
	20
	0

10	-4	10	-3	10	-2	10	-1	10	0	10	1
			IK-930 Concentration	(μM)
		TEAD gene			NF2 mutant mesothelioma
		expression			proliferation

Robust Inhibition

TEAD Target Gene Expression

CNN1

ANKRD1

CTGF

NPPB

AMOTL2

CYR61

DMSOIK-930

TEAD activated cell line

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IK-930 Monotherapy Has Potential Across Genetic Mutations in the Hippo Pathway

Comparable to panTEADi in NF2 Deficient Mesothelioma with Impact Across Tumor

Models for Hippo Pathways Genetic Alterations

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0

0 0

				Vehicle
	8	0	0	panTEADi
VolumeTumorAverage SEM)-(mm3+/
			75 mpk IK-930
	6	0	0
	4	0	0
	2	0	0
			0
			0	1	0	2	0	3	0
						Days of Treatment

Average Tumor Volume

(mm3+/-SEM)

2000

1500

1000

500

0 0

Vehicle
IK-930 30	mg/kg QD
IK-930 75	mg /kg QD
IK-930 200 mg/kg QD

5	10	15	20
	Days post treatment initiation

25

Average Tumor Volume (mm3+/-SEM)

2000

1500

1000

500

0 0

Vehicle

IK-930 75 mg/kg QD

5	10	15	20	25
	Days post treatment initiation

NF2 Deficient Mesothelioma Model

LATS1/LATS2 Mutated Mesothelioma Model

YAP1 Amplified HNSCC Model

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IK-930 Mechanism Drives TEAD1 into Tumor-Repressive Activity

Leveraging the two opposing states of TEAD through binding TEAD1 to inhibit palmytoilation and promoting VGLL4 interactions

Two Opposing States of TEAD

Activator with YAP1 or		Repressor with VGLL4
TAZ (palmitoylation		(palmitoylation
dependent)		independent)

IK-930 Leverages the TEAD Biology to Gain

Repressive Activity from Both State

YAP1/TAZ

TEAD2-4

AP1 e.g.

		IK-930
YAP1/TAZ		VGLL4
	TEAD1
	TEAD
	IK-930

Activator state

Repressor state

IK-930-TEAD1-VGLL4 complex blocks chromatin access for TEADs and other transcriptional activators

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