Oncternal Therapeutics : Corporate Presentation, July 2024

TA RG E T I N G

C A N C E R

N e w S c i e n c e . N e w C a n c e r T h e r a p i e s . N e w H o p e .

Company Overview - July 2024

ONCT Corporate Presentation July 2024

Corporate Highlights

ONCT-534: DUAL-ACTION ANDROGEN RECEPTOR INHIBITOR (DAARI)

• Sixth cohort (1200 mg once daily) fully enrolled in Phase 1/2 dose escalation study in R/R mCRPC
• Received Fast-Track designation from U.S. FDA
• Activity in preclinical prostate cancer models of androgen receptor inhibitor resistance, including LBD mutations, AR overexpression and AR splice variants such as AR-V7

ONCT-808: AUTOLOGOUS CAR T CELL THERAPY TARGETING ROR1

• Encouraging clinical activity in Phase 1/2 clinical study in aggressive B-cell NHL, including CD19 CAR T treatment failures
• Study is open and enrolling patients with protocol amendments
• Robust, efficient and scalable manufacturing process using closed system

ZILOVERTAMAB: POTENTIALLY FIRST-IN-CLASS MONOCLONAL ANTIBODY TARGETING ROR1
• Encouraging 100% PFS for patients with CLL and TP53 aberrations being further investigated
• Discussions ongoing with BTK inhibitor developers
MULTIPLE CATALYSTS WITHIN CASH RUNWAY PERIOD
• ONCT-534 Phase 1/2 dose escalation study in R/R mCRPC initial data in 3Q 2024
• ONCT-808 clinical data update in aggressive B-cell NHL in 3Q 2024
• Cash and short-term investments of $27.0M as of March 31, 2024, cash runway into Q1 2025	3
ONCT Corporate Presentation July 2024

Experienced Team

James Breitmeyer, MD, PhD	Richard Vincent	Salim Yazji, MD	Raj Krishnan, PhD	Chase Leavitt	Pablo Urbaneja
CEO, Co-founder, Director	CFO	CMO	CTO/CSO	General Counsel	SVP, Corporate Development
				Tang Capital
				Management

±7

David Hale	Michael Carter, MB	Jill DeSimone	Daniel Kisner, MD	Rosemary Mazanet, MD, PhD	Bill LaRue	Charles Theuer, MD, PhD	Robert Wills, PhD
Co-founder	Director	Director	Director	Director	Director	Director	Director
Board Chairman

ONCT Corporate Presentation July 2024

4

Robust Pipeline - Novel Product Candidates in Multiple Indications

Modality	Product Candidate	Indication	Preclinical	Phase 1	Phase 2	Phase 3
Dual-Action	ONCT-534	Prostate Cancer			Patients
AR Inhibitor
					Treated
ROR1	ONCT-808	Aggressive B-cell NHL			Patients
Cell Therapy	(Autologous CAR T)
					Treated
ROR1 mAb	Zilovertamab	Hematological Malignancies				Seeking
and Solid Tumors (ISTs)
						Partnership

ONCT Corporate Presentation July 2024

5

Table of Contents

ONCT-534:DUAL-ACTION ANDROGEN RECEPTOR INHIBITOR (DAARI)

ONCT-808: ROR1 TARGETED CELL THERAPY

ZILOVERTAMAB: MONOCLONAL ANTIBODY TARGETING ROR1 FINANCIAL INFO AND UPCOMING MILESTONES

ONCT Corporate Presentation July 2024

6

ONCT-534Dual-Action Androgen Receptor Inhibitor (DAARI)

Differentiated Mechanism of Action

• ONCT-534acts on both the N-terminal domain (NTD) and the ligand-binding domain (LBD) of the androgen receptor (AR) and induces AR protein degradation
• • NTD binding essential for activity against splice-variants
• Current standard of care treatments, such as enzalutamide or apalutamide, bind to LBD only

N-terminal Domain (NTD) DNA-binding Domain (DBD)

Ligand-binding Domain (LBD)

Hinge

Potential to address unmet needs in prostate cancer

• Potential next-generation treatment option for patients with R/R metastatic prostate cancer
• Compelling preclinical efficacy in vitro and in vivo
• • Activity against enzalutamide-sensitive and resistant models, including AR overexpression, LBD mutants, splice variants tumors
• Dose escalation portion of Phase 1/2 Study ONCT- 534-101 in patients with mCRPC ongoing; received Fast Track designation by U.S. FDA in October 2023
• Potential in other AR-driven disease, including luminal AR-triple negative breast cancer (LAR- TNBC) and non-oncology rare disease indication

ONCT Corporate Presentation July 2024

7

ONCT-534 Exhibits Anti-tumor Activity in an ENZA-Sensitive,AR-overexpressing VCaP Model in Castrated Male Rats

)

3

T u m o r V o l u m e ( m m

	V e h i c l e ( n = 5 )							1 0 0 0	V e h i c l e ( n = 5 )
								E n z a l u a t m i d e 3 0 m p k ( n = 5 )
	E n z a l u t a m i d e 3 0 m p k ( n = 5 )				)
1 0 0 0 0				e ( %
ONCT-534 60 mpk (n=5)					8 0 0	O N C T - 5 3 4 6 0 m p k ( n = 5 )
							o l u m	6 0 0
							V
							o r	4 0 0
5 0 0 0							m	** ** ** **
							u
		* ** **	**	**			i n T	2 0 0		** **
		** ** **		**	**		n g e	0	**
	**	**			C h a
0	** **				**1 0 ** ** **	2 0	3 0
			**
0	1 0		2 0	3 0		- 2 0 0	D a y s	** **** **
		D a y s
											**p<0.01

ONCT-534 is active against prostate cancer models expressing high levels of a native sequence AR

Ponnusamy, Clin Cancer Res 2019

ONCT Corporate Presentation July 2024

8

ONCT-534 Exhibits Anti-tumor Activity in ENZA-Resistant MDVR VCaP Model in Uncastrated Male Rats

C h a n g e i n T u m o r V o l u m e ( % )

3 0 0

2 0 0

1 0 0

0

- 1 0 0

M D V R - I n t a c t A n i m a l s

V e h i c l e ( n = 3 )

E n z a l u t a m

i d e ( n = 3 )

O N C T - 5 3 4

( n = 3 )

	1 0	**	** **		2 0	3 0
**
**		**
				**	**
			D a y s
					**p<0.01

ONCT-534 is active against enzalutamide-resistant MDVR prostate cancer model, even in the presence of normal androgen levels

ONCT Corporate Presentation July 2024

Oncternal company information

9

ONCT-534 Requires AR N-Terminal Domain For Protein Degradation

Conclusion:

• ONCT-534requires the AR N-terminal domain to induce AR degradation

AR		GR

AGG

GAA

ONCT-534 (µM) - 10 - 10

Ab: AR

Ab: GAPDH

AR AGG

AR/GAPDH (Fold) 1 0.2 1 0

- 10 - 10

Ab: GR

Ab: GAPDH GAA GR

1 0.9 1 0.8

Chimeric constructs of AR and GR (glucocorticoid receptor) were generated. ONCT-534 induced degradation of AR and AGG (AR-NTD,GR-DBD and LBD), but not GR and GAA (GR-NTD,AR-DBD and LBD).

ONCT Corporate Presentation July 2024

Ponnusamy, Clin Cancer Res 2019

10

ONCT-534 Induces Degradation of Native and Splice Variant AR, Mediated by Ubiquitination and Proteosomal Degradation

• ONCT-534induces degradation of both native AR and splice variant AR- V7
• ONCT-534inhibits growth and PSA level of AR-V7 expressing in vivo prostate cancer model

R1881 (0.1 nM)

ONCT-534 (µM) - - 0.1 1

Poly Ub-AR

AR

• ONCT-534binding to AR results in mono- and poly- ubiquitination

• AR degradation induced by ONCT-534 is inhibited by bortezomib, a proteosome inhibitor

ONCT Corporate Presentation July 2024

Ponnusamy, Clin Cancer Res 2019
& Oncternal company information	11