==> picture [539 x 73] intentionally omitted <==

15 December 2021

ASX Announcement

CASH POSITION, CARINA NEWS AND CORPORATE PRESENTATION

Key points:

Cash position of A$6.46 million at 30 November 2021 (excluding A$3.75 million Placement proceeds)
Research plan agreed for first target in Carina collaboration
Corporate presentation attached

MELBOURNE Australia, 15 December 2021: AdAlta Limited (ASX:1AD), the clinical stage biotechnology company developing novel therapeutic products from its i-body platform is pleased to announce a healthy, replenished cash position, progress on its collaboration with Carina Biotech and its current corporate presentation in addition to a successful institutional placement (Placement) announced separately today.

AdAlta's CEO, Dr Tim Oldham commented,

"AdAlta’s strengthened cash balance positions us well to maximise near term development milestones. The progress on AD-214 announced today and last week continue to support the potential efficacy of AD-214 in fibrotic diseases as well as the feasibility of a patient preferred, inhaled new treatment for Idiopathic Pulmonary Fibrosis and Interstitial Lung Disease. We have a number of development milestones planned for AD-214 during the first half of 2022 and the achievement of those is expected to steadily increase the value of AD-214 to partners. We also anticipate making meaningful progress on our two partnered programs with Carina and GE Healthcare during the same period.”

Cash position

AdAlta’s cash balance at 30 November 2021 was A$6.46 million (A$6.77 million at 31 October 2021), reflecting operating expenses for the quarter to date offset by the net A$0.89 million received from the Company’s annual R&D Tax Incentive (RDTI) rebate (announced November 2021). This is in addition to the A$3.75 million Placement announced separately today.

CAR-T program progress

AdAlta entered a collaboration agreement with Carina Biotech in August 2021 to develop precision engineered, i-body-enabled CAR-T (iCAR-T) cell products against five solid tumour targets. The two companies have now executed a research plan, with Carina Biotech to discover and develop iCAR-T cells against the first target under the collaboration. The iCAR-T cells are expected to be created in the first half of calendar 2022 with in vitro cytotoxicity results expected in the second half. The parties aim to finalise the research plan against the second target in the first quarter of calendar 2022.

Corporate presentation

AdAlta’s most recent corporate presentation is attached.

==> picture [595 x 83] intentionally omitted <==

==> picture [539 x 73] intentionally omitted <==

Authorised for lodgement by:

Tim Oldham CEO and Managing Director 15 December 2021

Notes

About AdAlta

AdAlta Limited is a clinical stage drug development company headquartered in Melbourne, Australia. The Company is using its proprietary i-body technology platform to solve challenging drug targeting problems and generate a promising new class of single domain antibody protein therapeutics with the potential to treat some of today’s most challenging medical conditions.

The i-body technology mimics the shape and stability of a unique and versatile antigen binding domain that was discovered initially in sharks and then developed as a human protein. The result is a range of unique proteins capable of interacting with high selectivity, specificity and affinity with previously difficult to access targets such as G-protein coupled receptors (GPCRs) that are implicated in many serious diseases. i-bodies are the first fully human single domain antibody scaffold and the first based on the shark motif to reach clinical trials.

AdAlta has completed Phase I clinical studies for its lead i-body candidate, AD-214, that is being developed for the treatment of Idiopathic Pulmonary Fibrosis (IPF) and other human fibrotic diseases for which current therapies are sub-optimal and there is a high unmet medical need.

The Company is also entering collaborative partnerships to advance the development of its i-body platform. It has an agreement with GE Healthcare to co-develop i-bodies as diagnostic imaging agents against Granzyme B, a biomarker of response to immunooncology drugs, a program now in preclinical development. It also has a collaboration with Carina Biotech to co-develop precision engineered, i-body enabled CAR-T cell therapies to bring new hope to patients with cancer.

AdAlta’s strategy is to maximise the products developed using its next generation i-body platform by internally discovering and developing selected i-body enabled product candidates against GPCRs implicated in fibrosis, inflammation and cancer and partnering with other biopharmaceutical companies to develop product candidates against other classes of receptor, in other indications, and in other product formats.

Disclaimer: This announcement and attachments may contain certain forward-looking statements that are based on subjective estimates and assumptions and relate to circumstances and events that have not taken place and may not take place. Such forward looking statements involve known and unknown risks, uncertainties, and other factors (such as significant business, economic and competitive uncertainties and contingencies, and regulatory and clinical development risks and uncertainties) which may cause the actual results or the performance of AdAlta Limited to be materially different from the results or performance expressed or implied by such forward looking statements. Past performance is not a reliable indicator of future performance. There can be no assurance

==> picture [595 x 83] intentionally omitted <==

==> picture [539 x 73] intentionally omitted <==

that any forward-looking statements will be realised. AdAlta Limited does not make any representation or give any warranty as to the likelihood of achievement or reasonableness of any forward-looking statements.

Further information can be found at: https://adalta.com.au

For more information, please contact:

Investors Media Tim Oldham, CEO & Managing Director IR Department Tel: +61 403 446 665 Tel: +61 411 117 774 E: [email protected] E: [email protected]

==> picture [595 x 83] intentionally omitted <==

Corporate overview December 2021

==> picture [344 x 450] intentionally omitted <==

INVESTOR PRESENTATION – DECEMBER 2021 2

==> picture [63 x 15] intentionally omitted <==

Disclaimer

Investment in AdAlta is subject to investment risk, including possible loss of income and capital invested. AdAlta does not guarantee any particular rate of return or performance, nor do they guarantee the repayment of capital.

This presentation is not an offer or invitation for subscription or purchase of or a recommendation of securities. It does not take into account the investment objectives, financial situation and particular needs of the investor. Before making any investment in AdAlta, the investor or prospective investor should consider whether such an investment is appropriate to their particular investment needs, objectives and financial circumstances and consult an investment advisor if necessary.

This presentation may contain forwardlooking statements regarding the potential of the Company’s projects and interests and the development and therapeutic potential of the company’s research and development. Any statement describing a goal, expectation, intention or belief of the company is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercialising drugs that are safe and effective for use as human therapeutics and the financing of such activities.

There is no guarantee that the Company’s research and development projects and interests (where applicable) will receive regulatory approvals or prove to be commercially successful in the future. Actual results of further research could differ from those projected or detailed in this presentation. As a result, you are cautioned not to rely on forward-looking statements. Consideration should be given to these and other risks concerning research and development programs referred to in this presentation.

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AdAlta today

AdAlta is building significant growth momentum while retaining agility to respond and adapt to data and opportunities

==> picture [56 x 56] intentionally omitted <==

i-body platform : can create therapeutics addressing targets underserved by traditional antibodies

==> picture [66 x 66] intentionally omitted <==

Fibrosis/inflammation: lead asset AD-214 preparing for Phase II clinical trial
US$3b Idiopathic Pulmonary Fibrosis (IPF) market today,[1] multiple US$b indication potential
Second target in discovery

==> picture [61 x 61] intentionally omitted <==

• Immuno-oncology: two co-development collaborations

GZMB PET imaging agent with GE Healthcare : US$6.4b PET imaging agent market[2]
• i-body enabled CAR-T with Carina Biotech : US$20b market by 2028[3]

==> picture [64 x 64] intentionally omitted <==

Continuing to build out pipeline with additional internal and external programs: targeting 10 by 2023
GlobalData, Idiopathic Pulmonary Fibrosis Opportunity Analysis and Forecasts to 2029, November 2020 2. 2027 forecast by Global Industry Analysts, Imaging Agents: Global Market Trajectory and Analytics, April 2021 3. 2028 forecast by Grandview Research, “T-cell Therapy Market Size, Share & Trends Analysis” Feb 2021

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Four human health needs AdAlta is addressing today Antibodies cannot do everything! AdAlta’s i-bodies are a new drug discovery platforms for challenging targets Idiopathic Pulmonary Fibrosis: degenerative, fatal AdAlta’s AD-214 could meet a desperate need for new approaches for a debilitating disease Immuno-oncology drugs revolutionising cancer treatment … for some AdAlta and GE Healthcare’s GZMB PET imaging could identify responders early CAR-T cell therapy providing new hope for blood cancer patients AdAlta and Carina’s i-body CAR-T cells could offer same hope for patients with solid tumours

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

What is the i-body advantage?

All the selectivity and specificity of antibodies with greater versatility and tunability

==> picture [463 x 297] intentionally omitted <==

----- Start of picture text -----

Accessing
challenging
targets
Small Molecule Antibody i-body
Diverse
applications
Naked PEGylation Fc-fusion Bi-specific Payload CAR cell
i-body targeting therapy
----- End of picture text -----

Small size, flexible binding domain Confers unique binding capability for targets challenging traditional antibodies; enables modular drug design across diverse applications

Minimising off-target side effects

Unique binding capability potentially allows greater selectivity and specificity, tunable affinity

Multiple drug administration routes

Amenable to multiple administration routes (e.g. injection, inhalation and topical)

Robust

Resilient to pH and temperature cycling

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

An immensely powerful drug discovery platform i-body technology can enable a wide range of therapeutic and diagnostic products

Wide range of target classes

Wide range of product formats

CAR-T

==> picture [574 x 227] intentionally omitted <==

----- Start of picture text -----

Targeting agents
Chemokine
That deliver
therapeutic cargos
more precisely
G-Protein Coupled
Lysophos-
>25 targets to which pholipid Receptors GZMB
Other i-body binders have i-bodies
been found
Neurotensin
Acetylcholine Direct therapeutics
Prostanoid For challenging targets,
Ion channel such as GCPRs
AD-214
----- End of picture text -----

Bi-specifics and multi-specifics

To improve targeting and selectivity

For challenging targets, such as GCPRs

==> picture [75 x 26] intentionally omitted <==

----- Start of picture text -----

AD-214
----- End of picture text -----

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AD-214: first in class treatment for fibrosis

AD-214’s initial focus is IPF

==> picture [654 x 309] intentionally omitted <==

----- Start of picture text -----

First-in-class (novel mode Human
of action) treatment
Lung
Tissue
Brown stain shows
increased amount of
Targets a receptor called CXCR4 in fibrotic
CXCR4 lung tissue
Normal Diseased
Initial focus is Idiopathic
Pulmonary Fibrosis
(IPF) , one of a group
Mouse
of Interstitial Lung
model of
Diseases (ILDs)
lung Purple stain
fibrosis shows amount
of collagen
(fibrosis)
Blocking CXCR4
reduces fibrosis in animal
models
Normal mouse IPF mouse lung tissue IPF mouse lung tissue
lung tissue + AD-214
----- End of picture text -----

IPF tissue images taken 21 days after bleomycin (BLM) was administered to induce fibrosis; mouse treated with AD-214 received 10 mg/kg AD-214 every 4 days from day 8 after bleomycin administration.

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AD-214: multiple indication extension options

Each additional indication could address multiple markets with US$ billion potential

Data in tissue and animal models show that AD-214 may improve fibrosis across a range of fibrotic diseases and cancer:

multiple indication extension potential

Indication specific formulations and routes of administration may enhance partnering potential

LUNG (lead indication - inhaled): Idiopathic Pulmonary Fibrosis with natural extension to Interstitial Lung Disease
EYE (intravitreal injection): Wet-Age Related Macular Degeneration
CANCER : 23 different cancers, enhancement of I/O drugs*
KIDNEY : Chronic kidney disease*
LIVER: NASH*
SKIN (topical, local injection) : Hypertrophic scars

==> picture [348 x 144] intentionally omitted <==

----- Start of picture text -----

Lung Eye Cancer
IPF/ILD Wet-AMD 23 different cancers, I/O
>US$3b >US$15b >US$1b ea
----- End of picture text -----

==> picture [351 x 171] intentionally omitted <==

----- Start of picture text -----

Liver Skin
Kidney
NASH & CIRRHOSIS SCLERODERMA
RENAL FIBROSIS
>US$10b
----- End of picture text -----

Subject to development of a satisfactory, improved intravenous formulation.

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Idiopathic Pulmonary Fibrosis (IPF)

AdAlta’s first target, already a $3b market, is a degenerative, fatal disease in dire need of improved treatment options: i-bodies have been designed to target a novel mode of action to address this medical need

In IPF, scarring and stiffening 3.8 years of the lungs progressively and median survival after diagnosis irreversibly reduces lung function

Despite being poorly tolerated and having difficult side effects, the two current therapies sell $3b per year

>300,000 people living with IPF, It is irreversible

40,000 people die from IPF every year

Burden of fibrotic lung disease following COVID-19 likely to be high.* “Long COVID” is a developing issue – potentially further increasing the need for better anti-fibrotic drugs.

PM George, et al, “Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy”, Lancet published online May 15, 2020.

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Phase I clinical and PET imaging inform dosing and route of administration

Intravenous AD-214 is well tolerated in Phase I studies; PET imaging with radiolabelled AD-214 supports early transition to inhaled route of administration

Phase I clinical study successfully completed[1]

Intravenous AD-214 is well tolerated in single and multiple doses

Direct lung delivery (inhalation) of AD ⁃ 214: a superior format for IPF

Target (CXCR4) binding observed with extended duration

Phase II studies in IPF scheduled for 2H 2023 with superior formulation

Resupply of AD-214 clinical material secured[2]

Defines timeline for Phase II clinical study

Improved intravenous formulation for other indications, derisks IPF

Pre-clinical intravenous studies inform optimal administration[3]

PET imaging shows rapid liver distribution (reduced bioavailability)
Preclinical animal data supports potential iv safety, efficacy profile
ASX Releases 10 Mar 2021 and 19 Jul 2021 2. ASX Release 1 July 2021
ASX Release 19 July 2021

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Key milestones progressively de-risk AD-214 development: IPF Phase II 2023

Quarterly milestones to de-risk formulation; extensive use of pre-clinical imaging; AD-214 partnering window from late 2022

==> picture [682 x 345] intentionally omitted <==

----- Start of picture text -----

Key data readouts
2021 2022 2023 2024
INHALATION
PROGRAM
✓ Aerosol stability and formulation
Pre-clinical efficacy, dose optimisation
Distribution, PK + imaging: correlated with efficacy
INTRAVENOUS
IV reformulation
PROGRAM
TOXICOLOGY
Multi-dose toxicology
PROGRAM
CLINICAL
PROGRAM Clinical: healthy volunteer bridging safety Bridging safety, PK
Clinical: patient Phase IIa/b
Patient imaging
CLINICAL
RESUPPLY Manufacturing (clinical resupply)
(SECURED)
PARTNERING Likely next AD-214 partnering window
PROGRAM
Calendar years
----- End of picture text -----

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Predicted regional deposition of AD-214 in human lungs

The ICRP66[1] model predicts that 17-46% of AD-214 delivered from commercial nebulisers will be delivered to the smallest (alveolar/interstitial) airways of the lungs where most IPF is found

		Device A	Device B
	Aerosol particle size (volume mean diameter)	4.8µm	4.4µm
	Fine particle fraction (% particles≤5µm)	55%	60%

	Deposition fraction
	Extra thoracic	17%	23%
	Tracheobronchial	8%	11%
	Bronchiolar	15%	11%
	*Alveolar / interstitial*	*46%*	*17%*
Exhaled fraction	Total lung(BB, bb, AI)	69%	38%
Extra thoracic fraction
Tracheobronchial fraction
Bronchiolar fraction	Exhaled	14%	38%
Alveolar/interstitial fraction

International Commission for Radiation Protection

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

IPF partnering: valuable options as early as Phase I

IPF assets have recently yielded attractive deal terms at early stages of development

Date	Transaction Terms	Asset/Mode of Action	Clinical Phase	Additional Comments
Nov-21	US$254m upfront	Cudetaxestat Autotaxin inhibitor	2 (Ready)	SPAC merger; Deal includes cudetaxestat (lead product) + calpain inhibitor products
Nov-21	€320m milestones	OATD-01 Chitotriosidase/acidic mammalian chitinase (CHIT1/AMCase) inhibitor	2 (Ready)	Single product license
Sep-21	US$152m upfront +US$602m milestones	Axatilimab CSF-1R inhibitor	2 (Ready)	Lead indication cGVHD
Nov-19	US$390m upfront +US$1b milestones	PRM-151 Recombinant form of human pentraxin-2 (PTX-2) protein.	2	Deal includes PRM-151 (IPF lead asset) + multiple assets for fibrotic diseases
Feb-21	US$517.5m milestones	TDI01 Rho containing protein kinase 2 (ROCK2) inhibitor	1	Single product license
Jul-19	€45m upfront +€1.1b milestones	BBT-877 Autotaxin inhibitor	1	Single product license

Source: Company press releases

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Immuno-oncology (I/O) PET imaging

US$6.4b PET imaging market: could help identify the 20-40% of patients who will respond to revolutionary I/O drugs faster

==> picture [167 x 308] intentionally omitted <==

Immuno-oncology (I/O) drugs reactivate the patient’s own immune system to fight cancer

Granzyme B (GZMB) is produced by immune cells to kill cancer Potential biomarker of immune system activated by I/O drugs

PET imaging agents have short development time

US$95 billion I/O market[1]

Only 20-40% of patients respond to I/O drugs[2]

PET imaging GZMB can help identify responders early

US$6.4 billion PET imaging agent market[3] Largest products >US$400m[4]

2026 forecast by ResearchandMarkets.com, Immuno-Oncology - Market Analysis, Trends, Opportunities and Unmet Needs - Thematic Research, March 2021 2. P Sharma, et al, Cell 168(4) 707 (2017)
2027 forecast by Global Industry Analysts, Imaging Agents: Global Market Trajectory and Analytics, April 2021 4. AD Nunn, J Nucl Med (2007) 169

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

GZMB i-body asset: GE Healthcare co-development collaboration

Second asset in pre-clinical development; and could generate royalty revenue sooner than a therapeutic due to shorter diagnostic development timelines

==> picture [103 x 30] intentionally omitted <==

Pipeline asset generating revenue for AdAlta

i-body discovery

Unique i-body platform

AdAlta earns research fees, development and sales milestone payments and royalties on product sales
Manufacturing process development
A$1.5 million revenue (milestones and research fees) earned to June 2021

==> picture [38 x 38] intentionally omitted <==

==> picture [122 x 31] intentionally omitted <==

October 2021 status

Panel of GZMB specific i-bodies identified

Leading global supplier of PET imaging equipment and tracers

18F chemistry, final product manufacture
Pre-clinical proof of concept studies underway
Manufacturing development underway
Pre-clinical, clinical proof of concept
Commercialisation

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

CAR-T therapies are revolutionising cancer treatment

Reprogramming a patient’s own immune system to fight cancer is a fast growing market at the cutting edge of medicine

==> picture [44 x 75] intentionally omitted <==

==> picture [171 x 187] intentionally omitted <==

----- Start of picture text -----

CAR engineeredchemokine
step 2 receptor
T cells genetically
modified to express
both the CAR molecule
+ chemokine receptor/s
----- End of picture text -----

step 1 T cells isolated from a patient’s blood

ü Takes advantage of the body’s natural immune response to pathogens
ü Immune cells removed from blood and reengineered so they “see” cancer as a pathogen

==> picture [49 x 85] intentionally omitted <==

==> picture [98 x 88] intentionally omitted <==

step 3 Newly created CAR-T cells expanded

step 4 CAR-T cells infused back into patient

earned by CAR-T therapy products in 2020[3]

US$1b

addressable patient 2m population within next 10 years[1]

US$20.3b revenue forecast for 2028[1]

solid tumour share of revenues by 2030[2]

50%

Grandview Research, “T-cell Therapy Market Size, Share & Trends Analysis” Feb 2021
Polaris Market Research, "CAR-T Cell Therapy Market Share, Size Trends, Industry Analysis Report", June 2021
Yescarta and Kymriah market size estimates calculated from various publicly available sources. Estimates vary and different analyses may give different results.

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

i-body enabled CAR-T assets: Carina collaboration

Third program entering discovery to generate precision engineered CAR-T products, providing new hope for patients with cancer

World-leading proprietary CAR-T technologies for superior access, potency and persistence

Unique i-body platform for exceptional reach and targeting capability

==> picture [96 x 95] intentionally omitted <==

==> picture [52 x 74] intentionally omitted <==

==> picture [95 x 40] intentionally omitted <==

==> picture [103 x 30] intentionally omitted <==

To develop precision engineered, i-body enabled, CAR-T therapies, including bi-specific and dual CAR-T products, that provide new hope for patients with cancer

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Building the first iCAR-T cell therapy: proof of principle results

i-body enabled CAR-T (iCAR-T) cells have been successfully generated by Carina and demonstrate in vitro cell killing (lysis)[1]

==> picture [657 x 183] intentionally omitted <==

Experimental details

LOVO and LIM1215 are colorectal cancer cell lines; U87 is a glioblastoma cell line
3 different Carina CAR-T constructs incorporating i-body against a single target “X” (CNA4002/CNA4003/CNA4004)
UT is an unmodified T-cell that does not result in significant killing (lysis) of these cell lines
i-CAR-T cells manufactured with 97% transduction (i-body CAR insertion) efficiency
i-CAR-T cells included 60-70% CD4+ (helper) and 20-30% CD8+ (cytotoxic – killer) T cells
210921 Carina iBody Datapack SB (2021) – previously unpublished data

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Carina collaboration details

AdAlta and Carina will jointly develop up to 5 targets to create CAR-T, bi-specific CAR-T and dual CAR-T cell therapy products

Up to 5 targets

Significant new, shared IP

Proof of principle already achieved ( in vitro )
Targets not yet disclosed

==> picture [46 x 46] intentionally omitted <==

Share costs, research to in vivo proof of concept
AdAlta + Carina will jointly own collaboration IP
Combine targets for bi-specific and dual-targeted CARs

Post proof of concept commercialisation options

Attractive deal space

Can continue to develop products together, progress independently or out license
Products emerge from the collaboration at proof of concept

==> picture [34 x 44] intentionally omitted <==

Biotech and immuno-oncology segment: very attractive deal space
Large biotech and pharma companies are actively sourcing CAR-T products

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AdAlta assets and business model

AdAlta’s pipeline is expanding to plan. The i-body platform is creating wholly owned or co-developed assets. Our team is building skills in fibrosis/inflammation and immuno-oncology.

Co- developed assets	Granzyme Bi-body enabledPET imaging agents for use in immuno-oncology	Precision engineered, i-body enabledCAR-T cells potentially providing new hope for patients with cancer	Immuno-oncology theme
	Pre-clinical	Discovery
			One more target
		to be added in early 2022
Wholly owned	Lead candidate: AD-214 First in class anti-fibrotic targeting CXCR4	Undisclosed target: GPCR for fibrotic disease	Fibrosis and inflammation
assets	Phase I	Discovery	theme
	Orphan Drug Designation for IPF
Platform	Patented, diverse i-body	discovery platform:
	20 billion different i-bodies for drugging undruggable targets

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

An expanding pipeline of i-body enabled products

==> picture [601 x 315] intentionally omitted <==

----- Start of picture text -----

IND
PROGRAM PARTNER PRODUCT/ DISCOVERY PRECLINICAL, ENABLING PHASE I PHASE II
INDICATION PRODUCT
STUDIES
DEV
CXCR4 AD-214: Idiopathic Inhaled
Pulmonary Fibrosis Intravenous
AD-214: Indication 2
Target 2 Not disclosed
Target 3 Not disclosed
Target 4 TBC
Target 5 TBC
GZMB PET imaging I/O
5 targets – i-body enabled, bi-specific
not disclosed and next-gen CAR-Ts
TBC Partner #3
TBC Partner #4
2020 Current End ‘21/early ‘22 End 2023 (aim)
INTERNAL PIPELINE
EXTERNAL PIPELINE
----- End of picture text -----*

Target #3 may be replaced by second Carina target, delivering shorter time to proof of concept

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

The potential of our strategy: Ablynx case study

Multiple internal and external assets drive value, attract partners

GPCR platform exits

==> picture [499 x 301] intentionally omitted <==

----- Start of picture text -----

Acquisition
US$5B
IPO
US$182m
+US$83m
+US$112m
+US$57m
+US$40m
+US$70m
IPO
US$121m
Global Data 2019
AdAlta is embarking on
a similar journey
----- End of picture text -----

Feb-15 acquired by Sosei Phase Ib + 7 preclinical leads US$400m Jul-15 acquired by Celgene Ph II/III + GPCR platform US$7.8b Feb-18 acquired by Sanofi 8 clinical, 37 preclinical candidates €3.9b

Source: Platinum Asset Management, AdAlta analysis

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Calendar 2022 goals

Significant progress anticipated on both existing core programs and further pipeline expansion

==> picture [46 x 44] intentionally omitted <==

AD-214 – first in class anti-fibrotic

Inhaled formulation development: nebulisation feasibility, efficacy in animal model of IPF (Q1); lung distribution imaging in healthy and disease model animals (Q1); dose finding and clinical formulation (Q2)
Intravenous formulation development (Q3)
GLP toxicology with inhaled formulation (commences 2H22)
Continuning partnering discussions (Q1); selection of next indication

==> picture [56 x 56] intentionally omitted <==

GE Healthcare – GZMB PET imaging

Pre-clinical proof of concept – milestone payment (mid-22)

==> picture [58 x 57] intentionally omitted <==

Carina Biotech – i-body enabled CAR-T cells

1st experimental results on Target #1
Commence i-body discovery on Target #2

==> picture [51 x 51] intentionally omitted <==

Internal pipeline and platform development

Initial functional data on i-body binders against internal Target #2 (2H22)
i-body2.0: new intellectual property filed (end’22)
7 programs in pipeline (end’22)
Additional patent filings, grants on individual i-body enabled products

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Industry experienced leadership and advisors

Team with experience from discovery through manufacturing, clinical and commercialisation

==> picture [63 x 62] intentionally omitted <==

==> picture [63 x 61] intentionally omitted <==

==> picture [63 x 60] intentionally omitted <==

==> picture [63 x 61] intentionally omitted <==

Board Dr Paul MacLeman Chair Liddy McCall Director (alt: Dr James Williams) Tim Oldham, PhD CEO & Managing Director Dr Robert Peach Independent Director

==> picture [75 x 22] intentionally omitted <==

Dr David Fuller Independent Director

==> picture [48 x 23] intentionally omitted <==

==> picture [47 x 23] intentionally omitted <==

==> picture [61 x 62] intentionally omitted <==

==> picture [61 x 60] intentionally omitted <==

Executive Scientific Advisory Board Tim Oldham, PhD Brian Richardson CEO & Managing Director Drug discovery and development expert Dallas Hartman, PhD Steve Felstead Chief Operating Officer Clinical development

==> picture [35 x 17] intentionally omitted <==

Claudia Gregorio-King, PhD VP Clinical Product Development

John Westwick

Pulmonary drug discovery and development Development team

==> picture [34 x 17] intentionally omitted <==

Mick Foley, PhD Founding Chief Scientist

10 staff (9 PhD’s)

==> picture [56 x 30] intentionally omitted <==

Skills in protein chemistry, i-body discovery, product development, pre-clinical development, clinical development

Michael Rasmussen Consultant Medical Expert

==> picture [54 x 23] intentionally omitted <==

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Corporate snapshot

Key financial details (15 Dec 2021 – proforma*)

	ASX code	1AD
	Market capitalisation	A$23.65m
	Share price (12 month closing range)	A$0.081 ($0.074 - 0.195)
	12 month return Ordinary Shares (daily volume) Unlisted Options Cash (30 Nov 2021)	(38)% 296,549,441 (426,207) 13,804,595 A$6.46m
	Proceeds ofplacement(14 Dec 2021)	A$3.75m

Major shareholders (15 Dec 2021 – proforma*)	%
Yuuwa Capital LP Platinum Asset Management	18.2 16.6
Meurs Holdings Pty Ltd	6.0
Radiata Super Pty Ltd	3.7
Sacavic Pty Ltd	2.5
Other (~1,600 total holders) Total	53.0 100%

Analyst Coverage

Pitt Street Research Lodge Partners

Share price performance (last 12 months)

==> picture [309 x 324] intentionally omitted <==

----- Start of picture text -----

0.25 7.0
6.0
0.20
5.0
0.15 4.0
3.0
0.10
2.0
0.05
1.0
0.00 0.0
19-Oct-20 19-Dec-20 19-Feb-21 19-Apr-21 19-Jun-21 19-Aug-21
Price Volume
Quarterly cash flows (A$ million)
Net inflows Net outflows Cash at end of quarter
12
10
8
6
4
2
0
(2)
(4)
(6)
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1
FY19 FY19 FY19 FY19 FY20 FY20 FY20 FY20 FY21 FY21 FY21 FY21 FY22
Volume (m)
Share price (A$)
Cash (A$ milion)
----- End of picture text -----*

Quarterly cash flows (A$ million)

*Proforma details incuding 15 December 2021 placementcommitments: market capitalization = closing market capitalization + placement commitments; issued shares and major shareholdings include shares subscribed in placement

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Investment proposition

==> picture [42 x 51] intentionally omitted <==

i-body platform to create value

==> picture [51 x 51] intentionally omitted <==

Clear vision for growth

==> picture [56 x 55] intentionally omitted <==

Fibrosis/inflammation Lead asset advancing to Phase II >$3b market potential in first indication[1]

Discovery initiated on 2[nd] target

==> picture [76 x 55] intentionally omitted <==

Leading expertise

Immuno-oncology 2 x co-development collaborations to leverage platform

ü GE Healthcare: $6b PET market[2] ü Carina Biotech: $20b CAR-T market[3]

Regular near-term news flow

GlobalData, Idiopathic Pulmonary Fibrosis Opportunity Analysis and Forecasts to 2029, November 2020 2. 2027 forecast by Global Industry Analysts, Imaging Agents: Global Market Trajectory and Analytics, April 2021 3. 2028 forecast by Grandview Research, “T-cell Therapy Market Size, Share & Trends Analysis” Feb 2021

Contact:

Tim Oldham, CEO and Managing Director [email protected] www.adalta.com.au

==> picture [344 x 450] intentionally omitted <==

Appendix: Strategy

==> picture [344 x 450] intentionally omitted <==

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Our strategy

==> picture [29 x 27] intentionally omitted <==

----- Start of picture text -----

A
----- End of picture text -----

i-body technology platform and library Proof of Principle against > 25 targets

==> picture [28 x 25] intentionally omitted <==

----- Start of picture text -----

B
----- End of picture text -----

In-house pipeline of drug candidates Usually GPCRs in fibrosis, inflammation, oncology Invest to value inflection (typically Phase I or II)

Licence to pharma Major upfronts + milestones and royalties

==> picture [43 x 73] intentionally omitted <==

Select novel, challenging drug targets where the i-body structure is most advantaged

Pharma, biotech partnerships Partner-led target selection and development Partner-enabled complex formats eg bivalent drugs

Co-develop with pharma, biotech Research fees + milestones and royalties

Multiple i-body drugs and diagnostics New drug class Potential in multiple disease indications

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AdAlta has successfully transitioned to the expansion phase of our growth plan

Accelerate (from ~mid-2021)

==> picture [28 x 30] intentionally omitted <==

Expand (~mid 2020 to late 2021)

==> picture [30 x 30] intentionally omitted <==

Maximise catalysts from current funded base (2020)

==> picture [216 x 52] intentionally omitted <==

From…

Via…

Towards 2023…

i-body platform in clinic for difficult drug targets
Clinical and commercial validation: AD-214 Phase I trial and GE partnership
Laying the foundations for growth
Progress AD-214
Build internal and external pipeline
Continuous platform improvement
Multi-product, multi-partner platform company
AD-214 partnering, new indications
~5 internal GPCR programs
3-5 co-development partnerships

Appendix: i-bodies

==> picture [344 x 450] intentionally omitted <==

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

i-bodies: next generation protein therapeutics

i-bodies are built on human protein scaffolds to mimic the properties of single domain antibodies

Generation of the i-body

==> picture [24 x 23] intentionally omitted <==

----- Start of picture text -----

1
----- End of picture text -----

==> picture [49 x 88] intentionally omitted <==

Shark antibody binding domain with unique long loop

Two binding loops are engineered onto 2 the human protein. These enable tight binding to the drug target and have a therapeutic effect

==> picture [114 x 64] intentionally omitted <==

A human protein that is structurally equivalent to the shark single domain antibody is the backbone or scaffold protein of the i-body

3 Each unique i-body has different binding loops. AdAlta’s i-body library has 10[10] unique i-bodies

i-body is the combination of a human protein that mimics the structural features of the shark antibody with unique long loop binding sites

The long CDR3 loop of the i-body confers exceptional targeting and binding properties, providing therapeutic access to drug targets that have evaded traditional monoclonal antibodies

Drug targets include G-protein-coupled receptors (GPCRs), currently the most heavily investigated class of drug targets in the body

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

An immensely powerful drug development platform

==> picture [303 x 262] intentionally omitted <==

Demonstrated i-body platform capability

G-protein coupled receptors (GPCRs)
Fibrosis, inflammation, oncology
Diagnostics (PET tracers; cancer imaging)
Chimeric antigen receptor (CAR) cell therapy

GPCRs are the most heavily investigated class of drug today and 80% of GPCR targets are yet to be effectively exploited

**Includes both i-body and VNAR/IgNAR formats

Appendix: AD-214

==> picture [344 x 450] intentionally omitted <==

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AD-214: development summary

==> picture [675 x 319] intentionally omitted <==

----- Start of picture text -----

✓ ✓ ✓ ✓ ✓ ✓
Validated target Novel mode of GMP Pre-clinical NHP GLP Phase I clinical
action, IP manufacturing efficacy toxicology trial
• CXCR4 • Patented • Fc-fusion format • Bleomycin • Very clean tox • Very well
• Player in CXCR4 i-body • CDMO: KBI mouse model of profile tolerated
inflammatory, antagonist Biopharma IPF • Half-life • High, extended
fibrotic • CXCR4 • IND-ready CMC • Ashcroft Score, supports weekly target
processes expressed on package gene dosing engagement
• Biomarker, diverse cell expression, • Sustained • Preclinical
prognostic types collagen receptor imaging guides
indicator • Inhibition of • Eye, kidney, occupancy route of admin-
fibrotic cell liver cancer PoC istration
migration
Pre-IND meeting:
Panel of pre-clinical studies “generally sufficient” to support an Investigational New Drug application
The Phase I trial design is “reasonable” ✓
Orphan Drug Designation: granted
----- End of picture text -----

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AD-214 inhibits key features of the fibrogenic pathway with novel MOA

==> picture [651 x 291] intentionally omitted <==

----- Start of picture text -----

Block fibrocyte recruitment Inhibit epithelial cell secretion of
into the damaged tissue pro-fibrotic factors and epithelial to
mesenchymal transition
Injury Entry
Entry
Inflammatory
mediators Neutrophil BM fibrocyte Resident fibroblast
EMT
Platelet Fibrosis Excess deposition
activation IL-1β of ECM
Macrophage
TGF-β
IL-13
TNF
Epithelial cell T cell Myofibroblast Wound
ECM repair
1 Clotting and 2 Inflammatory 3 Fibroblast migration, 4 Tissue remodeling
coagulation cell migration proliferation and activation and/or resolution Wound contraction
Modulate aspects of
inflammation Inhibit fibroblast migration Reduce ECM deposition
and differentiation during tissue remodeling
----- End of picture text -----

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AD-214 induced reduction in progression of fibrosis in mouse bleomycin model

==> picture [10 x 90] intentionally omitted <==

----- Start of picture text -----

Ashcroft Score
----- End of picture text -----

==> picture [301 x 254] intentionally omitted <==

Day 8 bleomycin (start of treatment)

AD-214 reduced Ashcroft Score with statistical significance compared to bleomycin treated mice at:

1-30mg/kg every second day
10-30mg/kg every fourth day

Wide range of dosing regimens can be used to test efficacy

10mg/kg every second day exhibited
effectiveness by most study parameters
Human equivalent dose: 1mg/kg (estimated)

AD-214 efficacy demonstrated in gold standard IPF disease model

Supportive of potential human therapeutic window beginning as low as 1mg/kg

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

AD-214 attenuates renal damage induced by unilateral ureteral obstruction

UUO induces an increase in Fibronectin, Col1 and Col3 gene expression and protein deposition in murine kidneys.

1 and 5mg/kg AD-214 by intraperitoneal injection every two days for 14 days to mice with UUO decreases gene expression of key extracellular matrix (collagen) markers

==> picture [371 x 110] intentionally omitted <==

Control
UUO
UUO + negative control i-Body
AD-214 at 5mg/kg i.p. (n=5-9. P<0.001 (1-way ANOVA)

==> picture [305 x 11] intentionally omitted <==

----- Start of picture text -----

Fibronectin Collagen 1 Collagen 3
----- End of picture text -----

Collagen 1 in kidneys

Collagen 4 in kidneys

==> picture [438 x 87] intentionally omitted <==

Cao et al 2021 (JCI accepted for publication)

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

NHP GLP toxicology: AD-214 safe

3 non-human primate studies completed Good Laboratory Practice (GLP) study to evaluate safety and toxicology

10mg/kg, 30mg/kg and 100mg/kg multiple doses over four weeks plus recovery (human equivalent dose 32mg/kg)

AD-214 well tolerated with no deaths, no AD-214-related clinical signs, no changes in a panel of clinical observations:

neurological function
body weight
ophthalmoscopy
• blood pressure
coagulation
urinalysis
electrocardiography
• respiratory function
organ weight
• macroscopic and microscopic findings

Minor, transient, completely reversible increase in total white cell and circulating CD34+ cells

Small, transient, completely reversible decrease in serum total protein and albumin at highest dose only (100 mg/kg)

ToxTox study results were in line with expectations and in keeping with previous studiesstudy results were in line with expectations and in keeping with previous studies

No major organ toxicity has been observed on repeat dosing at high doses No major organ toxicity has been observed on repeat dosing at high doses No suggestion of off-target toxicities No suggestion of off-target toxicities

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Non-human primate GLP toxicology: Phase I dose justification

Pharmacokinetics

Elimination half-life 22-29h
Human equivalent: ~71h (estimate)
AD-214vailable for >3 days

Pharmacodynamics

60% receptor occupancy* for 72h at >30mg/kg
Human equivalent: ~10mg/kg (estimate)
High receptor binding for >3 days

==> picture [155 x 145] intentionally omitted <==

==> picture [270 x 161] intentionally omitted <==

Supportive of human therapeutic dose window including 10mg/kg intravenously, weekly or every second week Supportive of human therapeutic dose window including 10mg/kg intravenously, weekly or every second week

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Intravenous AD-214 Phase 1 clinical and pre-clinical imaging programs

The Phase 1 program has demonstrated the safety and target engagement of intravenous AD-214 in healthy volunteers

Phase 1 protocol in healthy volunteers - COMPLETE

Objectives of Phase 1 Part A and B:

Part A Part B Objectives of Phase 1 Part A and B: • Top-line safety data Single iv dose, Multiple ascending iv dose, healthy volunteers (HV SAD) healthy volunteers (HV MAD) • Explore optimal dosing intervals 42 participants, 7 cohorts 8 participants • Support FDA IND applications for further studies in all CXCR4 indications 0.01-20 mg/kg dose 3 x 5 mg/kg (every 2 weeks) Pre-clinical Clinical (future) Objectives of PET imaging program:

Support FDA IND applications for further studies in all CXCR4 indications

PET imaging*

Effect of elevated lung CXCR4 on distribution of AD-214

Single and multi-dose in fibrotic diseases

Development of RL-AD-214 for PET imaging – complete

Correlation of AD-214 distribution with efficacy

Open label with standard of care**

Distribution and efficacy studies

Explore CXCR4 expression as potential biomarker

==> picture [78 x 55] intentionally omitted <==

Intravenous and inhaled administration Healthy and IPF disease models (mouse and large animal)

Safety of AD-214 in combination with standard of care**
Supported by a Biomedical Translational Bridge grant from Medical Research Future Fund and MTPConnect ** Includes pirfenidone, nintedanib or non-pharmacologic intervention.

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Intravenous AD-214 Phase I healthy volunteer results

Intravenous AD-214 is well tolerated in single doses to 20 mg/kg and multiple doses to 5 mg/kg*

AD-214 molecule is well tolerated in single and multiple iv doses (see Appendix for more detail)*

No dose limiting toxicities or adverse events of clinical concern in single doses to 20 mg/kg
Moderate infusion related reactions (IRRs) in 3 participants (2 drug, 1 placebo) receiving multiple 5mg/kg doses
Rapidly resolved at end of infusion
Appear formulation related
No concerning clinical laboratory results, no adverse liver or other organ function detected
HREC approved progressing to 10 mg/kg

AD-214 clearly engages the target CXCR4 receptor in vivo*

Dose dependent changes in biomarkers of CXCR4 engagement observed
High and extended duration of receptor occupancy on circulating T cells
Biomarker response consistent across multiple doses at 5 mg/kg – no evidence of tolerance

AD-214 iv pharmacokinetics are dose proportionate*

Peak and total AD-214 exposure increases in a dose proportionate or more manner to 20 mg/kg, consistent across multiple doses at 5 mg/kg
Elimination half-life 44±15 hours at 20 mg/kg
No evidence of tolerance or drug induced clearance
Rapid distribution from plasma observed at all doses, consistent with rapid increase/saturation of receptor occupancy and preclinical imaging
Multiple dose data subject to database lock and full statistical analysis; receptor occupancy data only available to 4 hours after end of third infusion; antidrug antibody data only available to 14 days after second infusion (pre third infusion)

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Intravenous AD-214 Phase I healthy volunteer study: safety findings

Single iv doses to 20 mg/kg (42 participants)

Multiple iv doses 5 mg/kg (8 participants)

No dose limiting adverse events
No serious adverse events
No concerning clinical laboratory results
Dose escalation steps completed without concern
Adverse events (AEs) were non-concerning
Predominantly mild
Three Grade 2 (moderate) AEs
No dose limiting adverse events
Safety Management Committee and Human Research Ethics Committee approved progression to 10 mg/kg
No serious adverse events
No concerning clinical laboratory results
Adverse events (AEs) profile supports safety of AD-214 molecule
Predominantly mild
Three Grade 2 (moderate) treatment related AEs
Infusion related reactions (IRRs) reported in three participants – resolved rapidly when infusion ended
IRRs linked to formulation
Observed in participants receiving both AD-214 (2) and placebo (1)
Trended to increasing intensity and frequency with subsequent doses
Not associated with changes in vital signs, clinical, physical or cytokines
Protocol amended to include standard antihistamine and corticosteroid treatment options

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Intravenous AD-214 Phase I healthy volunteer study: immune response findings

Single iv doses to 20 mg/kg (42 participants)

Multiple iv doses 5 mg/kg (8 participants)

Isolated instances of minor cytokine elevation
Transient and primarily low level of elevation of IL-6 and IL-8 in some participants (including placebos)
No clinically significant cytokine release
Antidrug antibodies: detected in 11 participants
Predominantly low titre
- Characterisation pending
No clinical symptoms related to immune response observed
Sporadic and primarily low level elevation of cytokines IL-6 and IL-8, sporadic increases in TNF-a and IFN-g
No clear association with IRRs or antidrug antibodies
Low level increases in IL-6 in many participants 24-48h post infusion
No clinically significant cytokine response and no link to IRRs or ADAs
Antidrug antibodies: detected in three participants after second dose
All low titre
One also reported IRR (association unlikely)
Characterisation pending
Third dose data pending

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Intravenous AD-214 pharmacokinetics increase proportionally with dose (single doses)

Maximum exposure, Cmax, increases in a dose proportional manner
Total exposure, AUC0-inf, increases in a more than dose proportional manner
• Elimination half-life t1/2 ~40h

AD-214 plasma concentrations (log and linear scale) Maximum and total plasma exposure

==> picture [320 x 192] intentionally omitted <==

Single ascending dose data presented as mean ± std dev

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Intravenous AD-214 pharmacokinetics

Maximum exposure, Cmax, and total exposure, AUC0-inf, increase in a dose proportionate manner and are consistent across multiple doses of AD-214 at 5 mg/kg, supporting absence of drug induced tolerance or clearance

==> picture [665 x 234] intentionally omitted <==

----- Start of picture text -----

Maximum and total plasma exposure - SAD Maximum and total plasma exposure – 5 mg/kg
Peak AD-214 plasma concentration Total AD-214 exposure
140 600
120
500
100
400
80
300
60
200
40
100
20
0 0
SAD MAD#1 MAD#2 MAD#3 SAD MAD#1 MAD#2 MAD#3
Cmax (ug/mL) Cmax (ug/mL)
----- End of picture text -----

Pharmacokinetic profile

Rapid distribution from plasma (consistent with rapid and high CXCR4 receptor occupancy and PET imaging distribution studies)
• Elimination half-life 44±15 h at 20 mg/kg
SAD = single dose at 5mg/kg; MAD#1/MAD#2/MAD#3 are first, second and third multiple doses at 5 mg/kg; data presented as mean ± std dev

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Transient white blood cell and blood stem cell increases indicate CXCR4 engagement

Observed in Phase I HV SAD*

Transient, dose dependent, increase in WCC and CD34+ counts at 4-12 hours consistent with CXCR4 blockade

WCC counts WCC counts at 4h CD34+ cell counts

==> picture [209 x 227] intentionally omitted <==

==> picture [208 x 220] intentionally omitted <==

Single ascending dose data presented as mean ± std dev

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Transient increase in SDF-1 (natural ligand of CXCR4) consistent with CXCR4 engagement

Transient increases in SDF-1 levels at 4 hours in some participants, returning to baseline at 24h consistent with CXCR4 blockade

==> picture [335 x 251] intentionally omitted <==

Single ascending dose data presented as mean ± std dev

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Biomarkers of CXCR4 receptor engagement at 5 mg/kg

Transient increases in blood biomarkers demonstrate consistent engagement of the target receptor, CXCR4 across multiple AD-214 doses

==> picture [672 x 332] intentionally omitted <==

----- Start of picture text -----

CD34+ cells
Biomarker data confirm single dose findings, consistent across 16
Placebo
multiple doses: no drug induced tolerance or accumulation 14
12 SAD
10 MAD#1
White blood cell counts (WCC), haematopoietic stem cell (CD34+) 8
MAD#2
counts and concentration of SDF-1 are biomarkers of CXCR4
6
engagement by AD-214 MAD#3
4
Profile of biomarkers is consistent across multiple doses at 5 mg/kg 2
100% T cell CXCR4 receptor occupancy achieved for at least 24h (data 0
not shown, maximum duration analysis pending) 0 10 20 30 40
Time after start of infusion (h)
CD34+ cells at 4h WCC at 4h SDF-1 at 4h
30 30 10000
8000
20 20
6000
4000
10 10
2000
0 0 0
Placebo SADMAD#1MAD#2MAD#3 Placebo SADMAD#1MAD#2MAD#3 Placebo SADMAD#1MAD#2MAD#3
(cells/uL)
Mean CD34+ cell count
WCC at 4h (10^9/L)
CD34+ cell counts at 4h (cells/uL) SDF-1 plasma conc at 4h (pg/mL)
----- End of picture text -----

SAD = single dose at 5mg/kg; MAD#1/MAD#2/MAD#3 are first, second and third multiple doses at 5 mg/kg; CD34+ and WCC data is shown at 8h for MAD#2

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Sustained high levels of CXCR4 receptor occupancy on T cells

==> picture [335 x 289] intentionally omitted <==

White blood cells naturally express CXCR4 in healthy individuals, providing an accessible surrogate for AD-214 target engagement or receptor occupancy (RO)

Understanding duration of RO is critical to inform dosing

Primary

70% CXCR4 RO at 7 days after 5-10 mg/kg infusion • >60% CXCR4 RO at 21 days after 20 mg/kg infusion*

• Duration of RO is considerably longer than PK profile

If replicated on CXCR4 receptors in fibrotic tissues, result supports extended dosing intervals despite relatively rapid clearance from circulation

Receptor occupancy was monitored for one week at all dose levels except 20 mg/kg (4 weeks)

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

PET imaging studies inform dosing and route of administration

PET imaging with radiolabelled AD-214 supports early transition to inhaled route of administration

Rapid liver distribution and clearance reduces bioavailability

==> picture [5 x 7] intentionally omitted <==

Consistent with pharmacokinetic profile and a first pass clearance mechanism

More than half administered dose not available to target site of action

Direct lung delivery of AD-214 could achieve a therapeutic dose at lower levels than intravenous delivery

CXCR4 binding capability retained, supportive of potential efficacy

==> picture [5 x 7] intentionally omitted <==

Consistent with observed biomarker, receptor occupancy and bleomycin mouse efficacy data

Liver distribution does not appear to affect safety profile

No localization in hepatocytes (responsible for metabolic activity in liver) Consistent with lack of observed changes in liver function or toxicity in toxicology and clinical studies

==> picture [5 x 7] intentionally omitted <==

Radiolabelled AD-214 will continue to be a useful development tool

Alternate intravenous formulations to be evaluated to improve bioavailability

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Phase II planned with inhaled formulation

Delivery of AD-214 by inhalation has potential to improve bioavailability, be more convenient for patients, be more cost effective, and improve partnering flexibility

==> picture [146 x 282] intentionally omitted <==

AD-214 delivered direct to fibrotic areas
• First pass liver clearance avoided
Improved bioavailability • Dosing schedule flexibility to optimise receptor coverage
• Self administration (no scheduled clinic
Greater patient convenience visits; freedom of movement) • Less invasive • Lower drug dose means lower cost of goods
Enhanced cost effectiveness • Lower healthcare costs for administration
• Potential to partner AD-214 by indication using different routes of
Diversified partnering options administration - broadens potential long term options

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Inhalation in IPF

Numerous drugs have been formulated for inhalation in IPF and respiratory disease, a substantial number of biologics are in development for inhalation and off-the-shelf devices are available for rapid translation from intravenous route

Inhalation used regularly in IPF and other respiratory diseases

Substantial number of biologics in development for inhalation*

Off-the-shelf devices for nebulization of liquid formulations

4 inhaled IPF therapeutics in development (Phase III) (Phase IIb)
2 marketed inhaled biologics
19 clinical stage inhaled biologics including

==> picture [44 x 24] intentionally omitted <==

(Phase I/II) (Pre-clinical, biologic)
IPF patients routinely inhale salbutamol and steroids for symptom relief
Inhaled therapeutics also marketed for asthma, COPD, cystic fibrosis
Several fragment antibodies
1 single domain antibody (nanobody)
Majority sized between 15-80 kDa (AD-214 73 kDa, single i-bodies 15 kDa)
Majority via solution for inhalation
Smart mesh nebulisers assist compliance, accuracy, drug efficiency
Low shear forces designed for biologics
Liquid formulations: potential to utilize AD214 intravenous formulation with minimal modification

==> picture [87 x 87] intentionally omitted <==

==> picture [77 x 77] intentionally omitted <==

W Liang et al , Pulmonary delivery of biological drugs, Pharmaceuticals 2020, 12, 1025

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

A clinician’s perspective on AD-214 results so far

Un-met need in IPF/ILD remains – need to progress new therapies
Research at The Alfred suggests if targeting CXCR4 works in IPF it may work in other ILD’s
AD-214 is well tolerated and ready to move forward into multi-dose studies in healthy volunteers and patients
The data is supportive of extending dosing interval to two weekly at least
AdAlta approach is methodical and appropriate
PET imaging strategy is particularly important as an innovative way to explore target engagement and mode of action in diseased tissue
Key insights anticipated from multidose and early patient studies (in addition to safety):

Prof Glen Westall leading respiratory and lung fibrosis specialist

CXCR4 receptor engagement in tissue
Nature of the anti-drug antibodies that are expected with a biologic

AdAlta Investor Briefing 10 March 2021

Further characterisation of biomarker responses: CD34+, white cells, SDF-1a

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

IPF late-stage clinical landscape: a narrow development field

AdAlta’s novel mode of action and Orphan Drug Designation expected to be attractive to partners as an alternative to, and in combination with other therapies

Drug	Mode of action	Phase	Orphan Drug Designation
PRM-151	Endogenous human protein that directs the immune cells called macrophages to turn off and reverse fibrotic processes	Phase 3 (Mono or combination therapy)	YES
Pamrevlumab	Human monoclonal antibody (mAb) that inhibits the activity of connective tissue growth factor (CTGF) to inhibit myofibroblast activation, collagen deposition and other pro-fibrotic factors	Phase 3 (Monotherapy)	YES
Inhaled Treprostinil	Small molecule analogue of prostacyclin that reduces pulmonary artery pressure through direct vasodilation of the pulmonary and systemic arterial vascular beds	Phase 3 (Supportive care/ symptom reduction)	YES
*AD-214*	i-body-Fc fusion protein blocking CXCR4 to inhibit inflammatory cell migration, epithelial to mesenchymal transition and fibrotic growth factor production, and deposition of collagen	Phase I	YES

INVESTOR PRESENTATION – OCTOBER 2021

==> picture [63 x 15] intentionally omitted <==

IPF clinical development landscape: narrow and narrowing development field AdAlta’s novel mode of action expected to be attractive to partners

DRUG	MODE OF ACTION	PHASE	ORPHAN DRUG DESIGNATION
Inhaled Treprostinil	Reduction in pulmonary artery pressure through direct vasodilation of the pulmonary and systemic arterial vascular beds	Phase 3	Yes
PRM-151	Endogenous human protein that directs the immune system to naturally turn off and reverse the process of fibrosis	Phase 3	Yes
Pamrevlumab	Human monoclonal antibody (mAb) that inhibits the activity of connective tissue growth factor (CTGF)	Phase 3	Yes
Lebrikizumab	Monoclonal antibody (mAb) that binds soluble IL-13 to reduce inflammation	Phase 2	Yes
Ianalumab	anti-B-cell activating factor (BAFF) receptor fully human monoclonal antibody	Phase 2	No
GB0139	Galectin-3 inhibitor administered by dry powder inhalation	Phase 2	Yes
CC-90001	Interferes with JNK (c-Jun N-terminal kinase), a protein that the body produces in various situations, with some evidence of participation in IPF	Phase 2	No
BI 1015550	A small molecule phosphodiesterase 4b inhibitor shown to have an anti-fibrotic effect in animal models	Phase 2	No
ND-L02-s0201	Oligonucleotide drug using HSP47 (Heat Shock Protein 47) siRNA, which moderates collagen synthesis and secretion that causes fibrosis	Phase 2	No
PLN-74809	Inhibits integrins to block TGF-β1 activation, thereby preventing the growth of fibrotic tissue within the lung	Phase 2	Yes
Jaktinib	Jaktinib is a JAK inhibitors interfere with the JAK-STAT signaling pathway	Phase 2	No

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

IPF partnering: pre-clinical assets have attracted partnerships

IPF assets have recently yielded attractive deal terms at early stages of development

Date	Licensee	Licensor	Transaction Terms	Asset/Mode of Action	Clinical Phase	Additional Comments
Aug-20			US$17m upfront +US$360m milestones	RXC006 Porcupine inhibitor	Preclinical	Single product license
~~IPF~~ Jan-20	~~artnerin~~	~~: valuable~~	~~otions as e~~ Upfront undisclosed +US$1b milestones	~~rl as~~ Multi-asset platform Interleukin-11 inhibitor for fibro-inflammatory disease	Preclinical	Platform for multiple fibrotic disorders
Pha Jul-19	~~p~~ se I (Cont	inued)	~~p~~ US$30m upfront +$US1.03b milestones	~~y~~ AI drug discovery platform for fibrotic disease	Preclinical

Source: Company press releases

Appendix: CAR-T

==> picture [344 x 450] intentionally omitted <==

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Advantages of CAR-T therapy

For patients, CAR-T therapies offer a potentially curative, single shot therapy that is precision engineered to find and kill cancer

==> picture [23 x 23] intentionally omitted <==

Can be curative

==> picture [22 x 22] intentionally omitted <==

Long lasting

Highly targeted

Even in patients whose cancers have returned after multiple prior standard therapies

Living therapy: a single treatment can attack cancer over months and then remain in the immune system long term to fight cancer cells that return

Precision engineered to engage with tumour cells and to minimise healthy tissue damage

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

CAR-T market opportunity

The CAR-T market formed in 2017, has already reached US$1b and is forecast to reach US$20b by 2028

Sales and market share growth for CAR-T products[3]

ü >$US1 billion earned by CAR-T therapy products in 2020
ü Revenue of $US20.3 billion[1] forecast for 2028 as more CAR-T cell products are commercialised and science evolves
ü New CAR-T product approvals to expand addressable patient population to 2 million within next 10 years[1]
ü Solid tumours to account for >50% of CAR-T revenues by 2030[2]

==> picture [375 x 221] intentionally omitted <==

Grandview Research, “T-cell Therapy Market Size, Share & Trends Analysis” Feb 2021
Polaris Market Research, "CAR-T Cell Therapy Market Share, Size Trends, Industry Analysis Report", June 2021
Yescarta and Kymriah market size estimates calculated from various publicly available sources. Estimates vary and different analyses may give different results. Estimated cost of goods US$58,200 (range $40,000-$106,000, 2018) with pricing outcomes/value based.

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Current approved CAR-T products

Five FDA approved CAR-T products for blood cancers generate strong revenues and are in high demand

Manufacturer Product Notable CAR-T UPenn and Novartis Gilead acquired Kite Gilead acquired Kite Celgene acquired Juno Celgene acquired Juno transactions Alliance Aug 2012[2] Aug 2017 US$11.9b[1] Aug 2017 US$11.9b[1] Jan 2018 US$9b; BMS Jan 2018 US$9b; BMS acquired Celgene acquired Celgene Jan 2019 US$74b[3] Jan 2019 US$74b[3] FDA approval August 2017 October 2017 July 2020 February 2021 March 2021 (acute lymphoblastic (large B cell lymphoma) (mantle cell lymphoma) (large B cell lymphoma) (multiple myeloma) leukemia, large B cell lymphoma) Revenue 2020[4] US$474m US$563m US$44m N/A N/A

https://www.businesswire.com/news/home/20210204006011/en/Gilead-Sciences-Announces-Fourth-Quarter-and-Full-Year-2020-Financial-Results 2. https://www.novartis.com/
https://www.celgene.com/newsroom/cellular-immunotherapies/celgene-corporation-to-acquire-juno-therapeutics-inc/
businesswire.com/news/home/20210204006011/en/Gilead-Sciences-Announces-Fourth-Quarter-and-Full-Year-2020-Financial-Results, novartis.com, celgene.com/newsroom/cellular-immunotherapies/celgenecorporation-to-acquire-juno-therapeutics-inc/

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Collaboration synergies

By joining forces, AdAlta and Carina access complimentary expertise to create a toolbox to address three main challenges facing solid tumour CAR-T therapies. AdAlta expands its pipeline and further validates the i-body platform

==> picture [44 x 44] intentionally omitted <==

Precision

Limited tumour-specific antigens – healthy tissue can be damaged

Incomplete expression of tumourantigens – tumour can escape

==> picture [89 x 30] intentionally omitted <==

i-bodies specifically designed to enable access to new, difficult antigens

Small size confers greater design flexibility, enabling bi-specific and dual CARs to enhance specificity

==> picture [44 x 44] intentionally omitted <==

Performance

Tumour mass hard to penetrate for immune cells

==> picture [67 x 25] intentionally omitted <==

Engineered Chemokine Receptor Platform directs CAR-T cells to and into solid tumours

==> picture [44 x 43] intentionally omitted <==

Persistence

Tumour secretes molecules that suppress immune cell activity

==> picture [67 x 25] intentionally omitted <==

Best practice manufacturing process (9 days, 90% efficiency) and Chemokine Receptor Platform make more robust, resilient CAR-T cells

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

i-bodies in CAR-T format

i-bodies are approximately half the size of the traditional CAR binding domain
Enables greater flexibility in CAR design
Ideally suited to bispecific CARs
i-bodies are specifically designed to target antigens considered difficult or intractable for traditional antibodies and CAR constructs
In vitro proof of principle established for i-bodies in a CAR-T platform (in collaboration with Carina Biotech)

INVESTOR PRESENTATION – DECEMBER 2021

==> picture [63 x 15] intentionally omitted <==

Advantages of i-body enabled CAR-T

i-body enabled CAR-T cells may demonstrate improved precision, performance and persistence, particularly in bi-specific and dual CAR-T cells

Delivering precision to difficult to treat cancers: bi-specific and dual-specific CAR-T cells

ü Targets 2 antigens on cancer cells
ü Reduces opportunity for tumour cells to be missed
ü Reduces chance of damaging healthy tissue

==> picture [453 x 179] intentionally omitted <==

----- Start of picture text -----

i-body enabled
mono / dual CAR i-body enabled
bi-specific CAR
engineered
engineered
chemokine
chemokine
receptor
receptor
----- End of picture text -----

==> picture [454 x 21] intentionally omitted <==

AI assistant

ADALTA LIMITED — Investor Presentation 2021

64247_rns_2021-12-14_0d8d4211-e0fd-4cef-b807-2f913e38156a.pdf

15 December 2021

ASX Announcement

CASH POSITION, CARINA NEWS AND CORPORATE PRESENTATION

Key points:

AdAlta's CEO, Dr Tim Oldham commented,

Cash position

CAR-T program progress

Corporate presentation

Tim Oldham CEO and Managing Director 15 December 2021

Notes

About AdAlta

Corporate overview December 2021

Disclaimer

AdAlta today

AdAlta is building significant growth momentum while retaining agility to respond and adapt to data and opportunities

• Immuno-oncology: two co-development collaborations

What is the i-body advantage?

Minimising off-target side effects

Multiple drug administration routes

Robust

CAR-T

AD-214: first in class treatment for fibrosis

AD-214’s initial focus is IPF

AD-214: multiple indication extension options

Each additional indication could address multiple markets with US$ billion potential

Idiopathic Pulmonary Fibrosis (IPF)

Phase I clinical and PET imaging inform dosing and route of administration

Phase I clinical study successfully completed[1]

Resupply of AD-214 clinical material secured[2]

Pre-clinical intravenous studies inform optimal administration[3]

Key milestones progressively de-risk AD-214 development: IPF Phase II 2023

Predicted regional deposition of AD-214 in human lungs

IPF partnering: valuable options as early as Phase I

Immuno-oncology (I/O) PET imaging

GZMB i-body asset: GE Healthcare co-development collaboration

Pipeline asset generating revenue for AdAlta

Unique i-body platform

October 2021 status

Leading global supplier of PET imaging equipment and tracers

CAR-T therapies are revolutionising cancer treatment

i-body enabled CAR-T assets: Carina collaboration

Building the first iCAR-T cell therapy: proof of principle results

Experimental details

Carina collaboration details

Up to 5 targets

Significant new, shared IP

Post proof of concept commercialisation options

Attractive deal space

AdAlta assets and business model

An expanding pipeline of i-body enabled products

The potential of our strategy: Ablynx case study

Calendar 2022 goals

Significant progress anticipated on both existing core programs and further pipeline expansion

AD-214 – first in class anti-fibrotic

GE Healthcare – GZMB PET imaging

Carina Biotech – i-body enabled CAR-T cells

Internal pipeline and platform development

Industry experienced leadership and advisors

John Westwick

Corporate snapshot

Key financial details (15 Dec 2021 – proforma*)

Analyst Coverage

Share price performance (last 12 months)

Quarterly cash flows (A$ million)

Investment proposition

Contact:

Appendix: Strategy

Our strategy

AdAlta has successfully transitioned to the expansion phase of our growth plan

From…

Via…

Towards 2023…

Appendix: i-bodies

i-bodies: next generation protein therapeutics

Generation of the i-body

An immensely powerful drug development platform

Appendix: AD-214

ADALTA LIMITED Investor Presentation 2021