Kazia Therapeutics : EVT801 Progress Update Presentation

1. Diversified, Clinical-Stage Oncology Drug Development Company

EVT-801: A clinical stage, first-in-class small molecule targeting tumor (lymph)-angiogenesis

Non-confidential deck

March 2024

NASDAQ: KZIA | Twitter: @KaziaTx

Forward-LookingStatements

This presentation contains forward-looking statements within the meaning of the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements involve substantial risks and uncertainties, not all of which may be known at the time. All statements contained in this presentation, other than statements of historical fact, including statements regarding our strategy, research and development plans, collaborations, future operations, future financial position, future revenues, projected costs, prospects, plans, and objectives of management, are forward-looking statements. Not all forward-looking statements in this presentation are explicitly identified as such.

Many factors could cause the actual results of the Company to differ materially from the results expressed or implied herein, and you should not place undue reliance on the forward-looking statements. Factors which could change the Company's expected outcomes include, without limitation, our ability to: advance the development of our programs, and to do so within any timelines that may be indicated herein; the safety and efficacy of our drug development candidates; our ability to replicate experimental data; the ongoing validity of patents covering our drug development candidates, and our freedom to operate under third party intellectual property; our ability to obtain necessary regulatory approvals; our ability to enter into and maintain partnerships, collaborations, and other business relationships necessary to the progression of our drug development candidates; the timely availability of necessary capital to pursue our business objectives; and our ability to attract and retain qualified personnel; changes from anticipated levels of customer acceptance of existing and new products and services and other factors.

Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, there can therefore be no assurance that such expectations will prove to be correct. The Company has no obligation as a result of this presentation to clinical trial outcomes, sales, partnerships, future international, national or regional economic and competitive conditions, changes in relationships with customers, access to capital, difficulties in developing and marketing new products and services, or marketing existing products.

In addition, the extent to which the COVID-19 outbreak continues to impact our workforce and our discovery research, supply chain and clinical trial

operations activities, and the operations of the third parties on which we rely, will depend on future developments, which are highly uncertain and cannot be predicted with confidence, including the duration and severity of the outbreak, additional or modified government actions, and the actions that may be required to contain the virus or treat its impact.

Any forward-looking statements contained in this presentation speak only as of the date this presentation is made, and we expressly disclaim any obligation to update any forward-looking statements, whether because of new information, future events or otherwise.

1

EVT801 is a highly selective VEGFR3 inhibitor, primarily inhibiting lymphangiogenesis (formation of new lymphatic vessels)

Highly selective for VEGFR3

Expected to minimise off-target toxicities

Inhibits lymphangiogenesis

Less potential for hypoxia-induced resistance

Very strong preclinical data package

Evidence of activity in a wide range of tumour types

Strong potential for immunotherapy combo

Evidence of synergistic activity with IO agents

Oral Presentation

Administered by mouth once or twice daily

Strong IP Protection

Composition-of-matter to 2032 / 2033 in most jurisdictions

Low Cost of Goods

Straightforward manufacture with excellent stability

Favourable Preclinical Toxicology

Limited evidence of toxicity in one-month GLP studies

In Clinical Development

Currently undergoing Phase 1 clinical trial in Europe

3

Targeting angiogenesis is a well-established approach in the treatment of cancer

Product

Company

Target

Indications

Annual Sales (US$)*

VEGF-A

VEGFRs

PDGFRs RAF kinases

VEGFRs

PDGFRs

VEGFRs PDGFRs c-Kit FGFRs

VEGFRs c-Kit PDGFRs

• Colorectal cancer
• Lung cancer
• Breast cancer
• Other cancers
• Hepatocellular carcinoma
• Renal cell carcinoma
• Thyroid cancer
• Renal cell carcinoma
• Gasto-intestinalstromal tumour
• Renal cell carcinoma
• Soft tissue sarcoma
• Renal cell carcinoma

$7 billion

$1 billion

$750 million

$1 billion

$400 million

*approximate, based on company filings and market data

4

Despite their proven efficacy, angiogenesis inhibitors are limited by several key challenges

Angiogenesis inhibitors work by reducing the formation of new blood vessels around the tumour, starving it of vital nutrients needed for tumour growth, and limiting its ability to spread elsewhere in the body

1

Tumour Hypoxia

Sustained tumour hypoxia activates adaptive mechanisms, leading to secondary resistance and tumour progression

2

Off-Target Activity

Most small molecule angiogenesis inhibitors have a broad range of pharmacological activities, leading to substantial toxicity (e.g. hypertension proteinuria & hand-foot syndrome)

Limited

Duration of

Effect

Significant Side Effects

5

EVT801: A differentiating anti-tumour approach

	Inhibition of tumour escape and metastasis
1	• Stabilisation of tumour vasculature
•	Inhibition of (lymph)-angiogenesis
	•	Avoidance of hypoxia decreases potential
		for metastatic spread

2

Increase in anti-tumour immune activity

• No impact on T-cells viability
• Increased infiltration of effector T-cells
• Reduction in immunosuppressive myeloid cells

3

Tumour Killing

• Direct effect on VEGFR3-expressing tumour cells (typically from endothelial origin, e.g. sarcoma)

6

EVT801 selectively inhibits VEGFR3

AvastinLucentis

(bevacizumab)(ranibizumab)

VEGF-B

VEGF-A

VEGF-D

VEGF-E

VEGF-C

Sutent (sunitinib)

Nexavar

(sorafenib)

Inlyta

(axitinib)

Votrient

(panzopanib)

7

VEGFR1

Signal Modulation

VEGFR2

Angiogenesis

Vasculogenesis

T-Cell Migration

VEGFR3

Cell Survival

(Lymph)-

angiogenesis

T-Cell Migration

EVT801

EVT801 has a unique mode of action compared to angiokinase inhibitors

Unique mode of action:

Characteristics		EVT801	Angiokinase inhibitors
Blood vessel normalization	• Tumour blood vessel normalization through avoidance of	• Tumour escape due to only transient tumour
	hypoxia decreases potential for metastatic spread	blood vessel normalization inducing hypoxia
	•	No impact on CD3+ T-cells proliferation	• Inhibition of CD3+ T-cell proliferation
Immune activity	•	Reduction in immunosuppressive cells (CD45+ PDL1+ & M2)	• Increase in immunosuppressive cells
	• Increase in pro-inflammatory macrophages (M1)	• Decrease of pro-inflammatory macrophages (M1)

Safety:	EVT801	Sorafenib

EVT801 does not induce hypertension in telemetered rats unlike sorafenib

• EVT801 does not induce any significant hypertension even after administration of 500mg/kg
• A singe administration of sorafenib from 10mg/kg produces dose-dependant and long-lasting increases in mean arterial pressure with a rapid onset of action

8

Current anti-VEGF agents have limitations

		Multi-VEGF
Target characteristic	EVT801	inhibitors
Potent small molecule VEGFR3 inhibitor
and TK panel		X
High selectivity over other VEGF receptors
Orally available
Effective as single agent in high VEGFR3
expression models
Potential companion diagnostic		X
Equipotent to sorafenib
Reduced hypoxia/necrosis		X
Well-tolerated in animal models
Reduce macrophage infiltration		X
No inhibition of T cell function		X
Potential for orphan status
Inhibits lymphangiogenesis		X

9

	Cellular in vitro IC50 (nM)
Compound	VEGFR2	VEGFR3
EVT801	241	21
EVT801 metabolite	424	37
Lenvatinib	58	390
Fruquintinib	568	2,097

• More potent on VEGFR3 than second generation mTKIs
• High cellular activity on VEGFR3 compared to key competitor compounds
• Active as single agent in range of models without inducing hypoxia
• Selective over GPCRs, ion channels, kinases
• Negative for Cytotoxicity, Ames, hERG, Cyp inhibition

Unlike many mTKIs, EVT801 does not inhibit CD3+ T-cell function

% Cells	Live Cells
	%

Compound (0 - 100uM)

• Sorafenib and axitinib inhibit T-cell proliferation
• EVT801 and its metabolite have no negative impact on T-cell viability and proliferation (as well as Lenvatinib)

10