Ikena Oncology : Corporate Presentation - April 2024

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Corporate Presentation

Q2 2024

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

• Multiple ongoing clinical trials with expected data readouts in the next 12-18 months
• Leaders in Hippo pathway with clinical stage TEAD1 inhibitor IK-930
• • Differentiated safety profile emerging from early clinical data & early signs of activity in EHE
  • Focused recruitment in mesothelioma and EHE; additional clinical data planned for 2H 2024
  • Broad combination potential including in EGFRm and RASm cancers, starting with osimertinib in NSCLC
• Novel MEK/RAF molecular glue IK-595with best in class potential
• • Potential for greater therapeutic index
  • Broad potential across RAF and RAS mutant cancers where prior MEK and RAF inhibitors have not succeeded
  • Cleared safety evaluation of first dosing cohort; dose escalation ongoing
• Closed 2023 with >$175M in cash; Runway into 2H 2026

2

Ikena Wholly-Owned Pipeline and Assets

Development Pipeline Focused on Targeted Oncology

Candidate

Target

IK-930

TEAD

IK-595

MEK-RAF

Interventions

IND Enabling

Phase 1

Later Stage Development

Indications

Monotherapy

Hippo-altered cancers including EHE, MPM, other NF2 altered tumors, and additional YAP/TAZ fusion tumors

Combination

IK-930+Osimertinib for EGFRm resistant NSCLC Additional combos combating therapeutic resistance to other targeted agents

Monotherapy

RAS and RAF altered cancers

Combination

Preclinical synergies with multiple agents

3

EHE: Epithelioid Hemangioendothelioma | MPM: Malignant Pleural Mesothelioma | NSCLC: Non-Small-Cell Lung Cancer

Targeting TEAD & the Hippo Pathway

IK-930

Targeting TEAD Can Address Diverse Patient Populations with High Unmet Need

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

GENETIC ALTERATIONS

Hippo Pathway Activity Triggers TEAD Transcription-Dependent Tumor Growth

NF2THERAPEUTIC

RESISTANCE

MST1/2
KRAS
			BRAF		CDK
											4/6
LATS1/2		MEK
			EGFR
						ALK
YAP1/TAZ

YAP1/TAZ	TEAD DEPENDENT	TUMOR GROWTH
	TRANSCRIPTION
TEAD1	TEAD2 TEAD3 TEAD4

• Multiple genetic alterations lead to pathway activation including NF2 loss of function mutations and YAP/TAZ fusions
• Pathway activated through therapeutic resistance to treatment with other targeted therapies
• Monotherapy clinically validated in the field with a panTEAD inhibitor in mesothelioma
• panTEAD inhibition leads to proteinuria which limits continuous target coverage
• IK-930designed to optimized therapeutic index by selectively targeting TEAD1 paralog
• IK-930demonstrates efficacy equivalent to panTEAD inhibition in mesothelioma models and superior safety in multiple species

5 EHE: Epithelioid Hemangioendothelioma; MPM: Malignant Pleural Mesothelioma.

Confidential

5

IK-930 Drives TEAD1 Toward a Transcriptional Repressive State

Promotes TEAD1/VGLL4 interaction which broadly blocks oncogenic gene expression

IK-930

Fit with

Cys405 of

TEAD1 C405 M403

TEAD1

IK-930	Obstructed
	with Phe/Tyr
	of other

Y413	TEADs

Two Opposing States of TEAD

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

IK-930 Leverages TEAD Biology to Gain Repressive Activity from Both States

I411

IK-930 is designed to selectively bind
TEAD1 while blocking TEAD oncogenic	IK-930-TEAD1-VGLL4 complex blocks chromatin access
activity across paralogs
for TEADs and other transcriptional activators
6	Confidential

6

IK-930 Preclinical Data Suggests Similar Efficacy to panTEADi with Differentiated Safety Potential

IK-930 Shows Preclinical Efficacy in

Mesothelioma Models Similar to panTEADi

NF2 Deficient Mesothelioma Model

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

IK-930 showed efficacy across multiple models with

different Hippo pathway alterations

IK-930 Does Not Result in Proteinuria at All Tested Doses in

Monkeys, in Contrast to panTEADi

IK-930 Monkey 28-day

panTEADi Monkey 28-day

Average urinary protein-to-creatinine ratios and histopathology in non-

human primates predicted a therapeutic index of less than one for panTEAD inhibitors and a broad therapeutic window for IK-930

7	Confidential

7

Current Status of IK-930 Phase 1 Clinical Trial

Dose escalation data from IK-930 phase I trial shows early signs of clinical benefit & safety advantages

Completed

Current

Next Steps

Expansion Indications

Hippo-altered
cancers including
EHE, MPM, other
NF2 altered tumors,
and additional
	Formulation B
YAP/TAZ fusion	Formulation B
tumors	Continued
			Bridging cohorts	escalation
Formulation A	Improved PK
confirmed
Dose Escalation

Option to backfill dose cohorts with targeted expansion indications

EHE

NF2d MPM

Other MPM

Other NF2 and/or YAP/TAZ tumors

First combination: Osi	Combination Therapy
Dose Escalation

IK-930 is designed to selectively bind TEAD1 while blocking TEAD

oncogenic activity across paralogs

Demonstrated preclinical efficacy equivalent to panTEAD in mesothelioma models and superior safety in multiple species

IK-930 does not result in proteinuria at all tested doses in

monkeys, in contrast to panTEAD inhibition

Favorable clinical safety profile seen in clinical dose escalation

8	Clinical data update planned for 2H 2024

Confidential8

IK-930 First Signs of Clinical Impact in EHE; Ultra Orphan Indication with No Standard of Care

Epithelioid hemangioendothelioma (EHE)

• 100% defined by Hippo pathway alterations
• 300 patients in the US per year
• No standard treatment
• • EHE can range from very indolent to rapidly growing tumors resistant to systemic therapy
  • Aggressive clinical symptoms
  • RECIST has limited value* in capturing changes to disease related symptoms (e.g. pain) and QOL changes

Additional Analysis to Better Qualify QoL Impact in IK-930 Program

• Centrally confirm YAP/TAZ fusions by RNAseq
• Characterize oncogenic mutations by WES
• Evaluate TEAD dependence and EHE transcriptional signatures by RNAseq
• Characterize ctDNA molecular response by PCR

All 7 EHE Dose Escalation Patients Demonstrating Initial Clinical

Benefit with IK-930 Treatment

7 out of 7 patients reached stable disease (SD)

3 out of 7 patients with SD experienced tumor shrinkage in multiple target and non-target lesions

3 out of 7 patients continue on treatment with time on IK-930 ranging from 18 to 26 weeks and ongoing

4 out of 7 patients had improvement of clinical symptoms and subjective improvement of QoL

4*ESMO 2021; Additional Sources: US IncidenceMS-2,Pg 28 NCCN 2023; EU Incidence Global Cancer Observatory 2020; NCCN Version 1.2023 Mesothelioma: Pleural; NCCN Patients Guidelines; Image 1_Types; Image 2_Location; Image 3_Asbestos; Brcic et al, 2020

9

Hippo Pathway is Implicated in Resistance to Multiple Targeted Therapies

IK-930 has the potential to combat resistance and expand the number of patients that could benefit from targeted therapies

Two Clinical Opportunities in EGFR Resistance	Case Study: Resistance Mechanisms to Osi in EGFRm NSCLC
		40%+ of patients with Osimertinib resistance have unidentified
		mechanisms and represent a significant unmet need
First Line	Post Resistance	Leonetti, et al., Br J Cancer, 2019
Combo with Osi	Emergence
First line osi combined	Treating with IK-930
with IK-930 to	post the emergence of
potentially prevent the	resistance - negatively
emergence of	selecting for
resistance	actionable mutations

Exploring both as potential paths in clinical program

Clinical supply agreement with AstraZeneca for osimertinib signed in 2022; first combo planned for clinical program

10	"The biggest hurdle to targeted cancer therapy is the inevitable emergence of drug resistance."		10
Lim, et al. Journal of Hematology & Oncology 2019	Confidential