ADALTA LIMITED — Investor Presentation 2021

Mar 21, 2021

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Building a pipeline of i-body enabled therapeutics Investor Presentation March 2021 AdAlta Limited (ASX:1AD) Tim Oldham, CEO and Managing Director enquiries@adalta.com.au

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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 forward-looking 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.

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AdAlta is rapidly becoming a multi-asset company

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4
Executing growth: creating multiple i-body-enabled assets
•
$8m $8 million cash at 31 Dec
• 2 new internal programs to start 2021
• One new external (co-development) program forecast for 2021
• Pipeline products: 5 by end 2021; 9 by end 2023
3
Lead external asset: GE Healthcare target in lead optimisation
•
$1.15 million milestones and research fees received to 31 Dec 2020
• Pre-clinical development expected to commence Q2 2021
2
Lead internal asset: AD-214 a first in class anti-fibrotic in Phase I clinical trial
• Supportive US FDA pre-IND meeting; Orphan Drug Designation for Idiopathic Pulmonary Fibrosis
• Excellent safety profile, sustained high receptor occupancy (Phase I single dose, healthy subjects)
1
Patented i-body discovery platform: unique, validated capabilities against difficult targets
• First fully human single domain antibody platform; first based on shark motif to reach the clinic
• Clinically and commercially validated
HV SAD data
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• Next generation improvements in progress to maintain technology leadership

3

i-bodies: designed for “difficult to drug” targets

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CDR3 CDR3
CDR1 CDR1
Shark
Human
Human
Human NCAM i-body
Shark VNAR Ribbon overlay
Domain 1 library
scaffold
scaffold (billions)
First fully human single domain Advantaged over traditional antibodies:
antibody scaffold unique target access and binding, many
possible formats
First shark motif scaffold in clinical >25 targets “hit”: GPCRs, ion channels,
trials enzymes, ligands, protein interfaces
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• Known as an IgNAR when coupled to a fibronectin scaffold

AdAlta has two strategies to create valuable assets from the i-body platform

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A In-house pipeline
Licence to pharma
of drug candidates Major upfronts + milestones
Usually GPCRs in fibrosis, & royalties
inflammation, oncology
Invest to value inflection
(typically Phase I or II)
i-body Multiple i-body
technology drugs and
Select novel, challenging drug
platform and targets where the i-body diagnostics
library structure is most advantaged New drug class
Proof of principle Potential in multiple
against >25 targets disease indications
B Pharma, biotech
Co-develop with
partnerships
pharma, biotech
Partner-led target selection
Research fees +
and development
milestones & royalties
Partner enabled complex
formats eg bivalent drugs
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Lead asset AD-214: first-in-class anti-fibrotic

CXCR4 receptor is critical player in development of fibrosis in many organs

AD-214 is first in class: the only CXCR4 antagonist being developed for fibrosis

Normal Diseased Brown stain shows amount of CXCR4

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Potential in multiple fibrotic and cancer indications

• AD-214 specifically designed for fibrosis Novel pharmacology – active on multiple cell types implicated in fibrosis Granted patents expire 2036

Efficacy demonstrated in gold standard Idiopathic Pulmonary Fibrosis (IPF) mouse model

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Normal mouse lung tissue

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IPF mouse lung tissue (21 days after bleomycin [BLM])

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IPF mouse lung tissue + AD-214 (21 days after BLM; AD-214 at 10mg/kg every 4 days from day 8)

6

Phase I program studies healthy volunteers and patients

Phase 1 protocol in healthy volunteers

• Part B commences Q2 2021

• Part A: HV SAD Part B: HV MAD • Treatment complete end 2021

• Blinded/placebo controlled Blinded/ Placebo controlled • Safety data supports Phase II/

• 0.01-20 mg/kg single dose ✓ 5-15 mg/kg every 2 weeks FDA IND application in all AD-214 7 cohorts, 42 pts 3 cohorts, 12 – 24 pts indications (iv route)

Phase 1b protocol in patients with IPF/ILD and other fibrotic diseases

• Protocol in preparation*

• Anticipated to commence (with first images) Q3 2021

• Demonstrates AD-214 distribution and CXCR4 receptor occupancy in tissue

• Determines impact of disease on PK and RO parameters of AD-214

• Multiple CXCR4 mediated indications in combination with SoC**

• Multi-dose arm approaches Phase II treatment duration

Arm 1: PET screening of fibrotic diseases Open label with SoC 1-2 PET-CT sequences ~12 patients (~6 IPF/ILD) CXCR4 disease Arm 2: Multi-dose in IPF/ILD Open label with SoC Max 6 doses, 5-10mg/kg over 18 weeks ~6 patients +/- PET imaging

• Supported by Safety Management Committee, subject to HREC approval

7

** Standard of Care (includes pirfenidone, nintadanib or non-pharmacologic intervention)

Preliminary healthy volunteer single dose results

AD-214 has an excellent safety profile

• No dose limiting toxicities or adverse events of clinical concern

• No concerning clinical laboratory results

• Consistent with Non-Human Primate (NHP) toxicology studies

AD-214 engages the CXCR4 receptor

• Clear markers of target (CXCR4) engagement observed

Receptor occupancy sustained at high levels for extended periods

• Supportive of longer dosing interval than projected from NHP if replicated in patients

Enabled redesign of remainder of Phase I program to:

• Explore more clinically convenient dosing interval

• Deliver Phase II IND ready safety for multiple indications

• • Explore multiple doses in patients over longer period

8

Single dose of AD-214 is well tolerated

Adverse events (unblinded data)

Immune response*

• No dose limiting adverse events

• No serious adverse events

• Isolated incidences of minor cytokine elevation - Transient and primarily low level elevation of IL-6 and IL-8 in some participants (including placebos)

• No concerning clinical laboratory results

• No clinically significant cytokine release

• Dose escalation steps completed without concern

  • Antidrug antibodies: detected in 11 participant

    • Predominantly low titre

    • Characterisation pending

• Adverse events were non-concerning

• Predominantly mild

• No clinical symptoms related to immune response observed

• Three Grade 2 (moderate) adverse events

Pharmacokinetics

• Peak and total AD-214 exposure increases in a dose proportional or more manner to 20 mg/kg

• • Elimination half-life 44 15 hours at 20 mg/kg±

• Based on unblinded data, active drug participants assumed to be those for whom pharmacokinetic Cmax was determined

9

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

Observed in NHP GLP toxicology

• Transient increase in white cell counts (WCC) and

• blood stem cell (CD34+) cell counts

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Observed in Phase I HV SAD*

• Transient, dose dependent, increase in WCC and

• CD34+ counts at 4-12 hours consistent with CXCR4 blockade

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WCC counts WCC counts at 4h CD34+ cell counts
30 Placebo 30
Placebo
0.01mg/kg 30
25 0.02mg/kg 25 0.01mg/kg
0.02mg/kg
0.1mg/kg
20 1.0mg/kg 20 20 0.1mg/kg
1.0mg/kg
5.0mg/kg
15 10mg/kg 15 5.0mg/kg
10mg/kg
20mg/kg
10 10 10 20mg/kg
5
5
0
0
0
0 50 100
0 50 100 Time after start of infusion (h)
Time after start of infusion (h)
Placebo0.1mg/kg1.0mg/kg5.0mg/kg10mg/kg20mg/kg
Mean white cell count (X10^9/L) Mean viable cell count (cells/uL)
Mean white cell counts (x10^9/L)
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10 * Based on unblinded data, CD34+ incudes only participants for whom pharmacokinetics Cmax was determined
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Sustained high levels of CXCR4 receptor occupancy on T cells

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Mean occupancy of T cell CXCR4 receptors by
AD-214
120 0.01mg/kg
0.02mg/kg
1 week 0.1mg/kg
100 1mg/kg
5mg/kg
80 10mg/kg
20mg/kg
LLOQ
2 weeks
60
3 weeks
40
4 weeks
20
0
0 200 400 600
Time since end of infusion (h)
Percent receptor occupancy
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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

Observed in NHP GLP toxicology

• 50% CXCR4 receptor occupancy (RO) on T cells at four

• days after infusion of 10-20 mg/kg

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Observed*

• Dose dependent level and duration of RO

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• 70% CXCR4 RO at 7 days after 5-10 mg/kg infusion

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• 60% CXCR4 RO at 21 days after 20 mg/kg infusion**

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• Duration of RO is considerably longer than PK profile

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

• Based on unblinded data, incudes participants for whom PK Cmax was determined, placebo excluded ** Receptor occupancy was monitored for one week at all dose levels except 20 mg/kg (4 weeks)

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Lead indication IPF: $3b market, poor options

Idiopathic Pulmonary Fibrosis (IPF) is irreversible, unpredictable, incurable >300,000 people living with IPF 40,000 people die from IPF every year 3.8 years median survival after diagnosis Current treatments come with safety, efficacy limitations

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Burden of fibrotic lung disease following COVID-19 likely to be high “Antifibrotic therapies could have value preventing severe COVID-19 in IPF patients and preventing fibrosis after SARS-CoV-2 infection”*

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

Limited (and decreasing) new options for patients

FDA Fast FDA Orphan Phase II Phase III Track Drug ISABELA 1&2: TERMINATED 12 weeks, 23 subjects ✓ GLPG1690 52 weeks, 1500 subjects ZEPHYRUS - ACTIVE 48 weeks, 103 subjects ✓ ✓ Pamrevlumab 52 weeks, 565 subjects NO PROGRESS SINCE 2018 PBI-4050 12 weeks, 40 subjects ✓ ✓ Phase III initiated in 658 24 weeks, 116 subjects ✓ ✓ PRM-151 subjects - acquired by Roche NOT PROGRESSING 24 weeks, 76 subjects ✓ KD025 Focusing on other indications New therapies and combination therapies addressing multiple modes of action are required

13

Multiple options in play for AD-214

Phase I/Ib data

• Safety

• PK

• Receptor occupancy

• Receptor distribution

Early partnering options

Indication extension options

• IPF/ILD Phase II and other fibrotic indications

• Active early stage partnering landscape

• Metastatic cancer, I/O combinations

• Novel mode of action expected to be attractive

• First partnering window end of Phase I

• Animal data in >5 additional indications

• Markets worth US$2-15 billion each

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Jul-19 license by Boehringer
Ingelheim €45m + €1.1b
Phase I
Lung Eye Liver
IPF Wet-AMD & PVR NASH & CIRRHOSIS
Nov-19 acquired by Roche
$390m + $1b – Phase II
Aug-15 BMS option to buy
$150m + $1.25b milestones
Jan-20 platform license by
Boehringer Ingelheim Kidney Skin Heart
$?m + $1b milestones RENAL FIBROSIS SCLERODERMA CARDIAC FIBROSIS
Preclinical
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14

External pipeline: multi-national GE Healthcare

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i-body Target:
October ‘20 status
platform granzyme B • Panel of i-bodies identified
•
Lead optimization underway (6 mo)
•
A$1.15 million milestones and
research fees earned to date
Discovery
Development
Further milestones and royalties to be
earned on development and
commercialization success:
pipeline asset at no financial risk to
Commercialisation AdAlta
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Opportunity: PET imaging GZMB

• US$100 billion immuno-oncology market by 2025

• ~30% patients respond; granzyme B (GZMB) a biomarker for responders

• PET imaging GZMB could significantly improve therapy selection, outcomes

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Single domain antibody platform potential: Ablynx case study

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Ablynx strategy (2007) A. Leverage platform to rapidly identify potential drug candidates B. Drive lead product candidate through clinical development

C. Selectively partner to maximize market opportunity D. Maintain and expand technology and IP position

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Comparator position: year first product reaches clinic Opportunity : using first clinical trial as catalyst for acceleration

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Source: Ablynx Euronext IPO prospectus, NASDAQ prospectus and press releases; AdAlta analysis

Clinical validation of i-body platform unlocks pipeline expansion opportunities

November 2019

November 2020

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End 2021 (est) End 2023 (aim)

Preclinical, IND Class of Partner Product/ Indication Discovery product enabling Phase I Phase II Target Target dev studies Internal pipeline AD-214 : Idiopathic CXCR4 GPCR Pulmonary Fibrosis AD-214 : Indication 2 AD-214 : Indication 3 Target 2 GPCR Not disclosed Target 3 GPCR Not disclosed Target 4 GPCR TBC Target 5 GPCR TBC External pipeline Serine GZMB PET imaging I/O protease TBC TBC Partner #2 TBC TBC Partner #3 TBC TBC Partner #4

17

Milestones for remainder of 2021

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Mar ‘21
Phase Ib
Safety, PK, RO FDA pre-IND Ph I Part A Ph I HV SAD commences 1 [st] partnering
in NHP advice safety update top line safety 1 [st] PET images window opens
Efficacy in BLM Ph I Part A FDA ODD PET tracer Ph I HV MAD Ph I HV MAD
mouse commenced in IPF pre-clinical commences top line results
Jan Apr Jul Oct Jan Apr Jul Oct
2020 2021
Growth $8.1m 2 [nd] external 2 new internal i-body2.0
strategy placement, partnership targets in complete
update rights issue discovery
GE progress to GE progress to GE commence pre-
Stage 3 lead optimisation clinical development
AD-214
Other assets
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Industry experienced leadership and advisors

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

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Scientific Advisory Board
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Brian Richardson Drug discovery and development expert

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Steve Felstead Clinical development

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John Westwick Pulmonary drug discovery and development

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Executive
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Dallas Hartman, PhD Chief Operating Officer

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Claudia Gregorio-King, PhD VP Clinical Product Development

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Mick Foley, PhD Chief Scientific Officer

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Kevin Lynch, MD Consultant Medical Expert

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19
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Healthy cash position, supportive shareholders

Key financial details(12 Mar)
ASX code	1AD
Market capitalisation	A$44.4m
Share price_(12 month range) Ordinary Shares(daily volume)_	A$0.185_($0.04-0.21) 245,175,853(629,809)_
Listed Options	23,348,803
Unlisted Options	7,514,067
Cash(31 Dec 2020)	A$8.08m

	Major shareholders(8 Feb)	%
	Yuuwa Capital LP	22.0
	Platinum Asset Management	11.6
	Meurs Holdings Pty Ltd	7.3
	CS Third Nominees Pty Ltd	2.8
	Radiata Super Pty Ltd	1.9
	Other(1,399 total holders)	54.4
	Total	100%

Share price performance (last 12 months)

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0.25 7.00
6.00
0.20
5.00
0.15 4.00
0.10 3.00
2.00
0.05
1.00
0.00 0.00
Series1 Series2
12-Mar-2012-Apr-2012-May-2012-Jun-2012-Jul-2012-Aug-2012-Sep-2012-Oct-2012-Nov-2012-Dec-2012-Jan-2112-Feb-2112-Mar-21
Volume (m)
Share price (A$)
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Quarterly cash flows (A$ million)

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Net inflows Net outflows Cash at end of quarter
12
10
8
6
4
2
0
(2)
(4)
(6)
(8)
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2
FY19 FY19 FY19 FY19 FY20 FY20 FY20 FY20 FY21 FY21
A$8.1m capital raise, 69% from
existing register
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AdAlta (ASX:1AD) investment proposition

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Patented, validated i-body platform for asset creation: designed for “difficult” targets

• Unique properties to address targets that challenge traditional antibodies

AD-214: clinical stage first-in-class asset for fibrosis

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• Orphan Drug Designation for US$3 billion idiopathic pulmonary fibrosis (IPF) market

• Excellent safety profile and sustained high receptor occupancy in Phase I single dose studies

• Multi-dose studies commencing; PET images in patients Q3-2021; partnering window end of 2021

• Pre-clinical data available and emerging in multiple fibrotic indications and cancer

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GE Healthcare: commercial validation of platform

• Partner funded discovery program in I/O imaging; completinglead optimisation

Clear vision for growing existing assets and adding more; A$8m cash balance

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• AD-214: Phase I patient data, expand indications, partner

• Internal pipeline: GPCRs in fibrotic, inflammatory disease and cancer (2 new assets by end 2021)

• External pipeline: partner selected and funded targets: 2[nd] partnership by mid-2021

• Platform leadership: continuous improvements to i-body platform, formulation and manufacturing

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Experienced drug development team driving strategic focus

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Unique investment opportunity: validated platform, cash runway, beginning to realize expansion potential

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21
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Contacts for more information: Tim Oldham, CEO and Managing Director enquiries@adalta.com.au www.adalta.com.au

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APPENDIX

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

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Inhibit epithelial cell secretion
Block fibrocyte recruitment of pro-fibrotic factors and epithelial
into the damaged tissue to mesenchymal transition
Adapted from
Wynn
JEM 2011
Modulate aspects Inhibit fibroblast migration Reduce ECM deposition
of inflammation and differentiation during tissue remodeling
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24
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CXCR4 is expressed in both IPF and ILD patient lung tissue and in multiple cell types

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• CXCR4 was abundantly expressed in both IPF and ILF donors compared with non-diseased controls

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• CXCR4 is expressed on circulating immune cells and we have demonstrated that in patients with IPF and other fibrotic ILDs, CXCR4 is significantly upregulated in fibrotic airway epithelial cells and myeloid cells in fibrotic loci

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CXCR4 stained brown

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25 Source: Jaffar et al, Respiratory Research (2020) 21: 221
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AD-214: road to the clinic

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6
120100 Receptor Occupancy - All animals Vehicle10 mg/kg30 mg/kg100 mg/kg 54 ns Statistical significance ns ns ns * [#] to 21d bleomycin * ** **
80 3
60
40 2
20 1
0 0
-20
Pre-Dose 2 hours 48 hours 72 hours Pre-Dose 2 hours 48 hours 72 hours
post-SOI post-SOI post-SOI post-SOI post-SOI post-SOI
Normal Diseased i-body Fc-fusion Day 1 Day 25 Bleomycin alone Every 2 days Every 4 days
AD-114 AD-214 AD-214
Validated Novel mode of GMP NHP GLP
✓ ✓ ✓ ✓ ✓ In vivo efficacy
target action, IP manufacturing toxicology
CXCR4 Patented Fc-fusion Very clean Bleomycin
CXCR4 format tox profile mouse
i-body model of
antagonist IPF
Player in CDMO: KBI Half-life
inflammatory, CXCR4 Biopharma supports Ashcroft
fibrotic expressed weekly Score, gene
processes on diverse dosing expression,
cell types collagen
IND-ready Sustained
Biomarker, Inhibition of CMC receptor Eye, kidney,
prognostic fibrotic cell package occupancy liver cancer
indicator migration PoC
Percent receptor occupancy Ashcroft Score
Naïve 21 day 30 mg/kg 30 mg/kg 60 mg/kg 0.01 mg/kg 1 mg/kg 10 mg/kg 30 mg/kg 10 mg/kg 30 mg/kg
Control i- body Pirfenidone daily Nintedanib daily
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Panel of pre-clinical studies “generally sufficient” to support an Investigational New Drug application The Phase I trial design is “reasonable”

Pre-IND meeting Specific guidance readily incorporated into Phase I protocol and ongoing development plans

26

FDA engagement: AD-214

• Pre-IND meeting June 2020 Orphan Drug Designation granted for AD-214 in IPF February 2021

• • Pre-clinical studies “generally sufficient” to support an IND application

• • Phase I trial design is “reasonable”

• • Minor feedback readily incorporated into clinical trial design and ongoing preclinical and CMC studies

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27

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

	Naïve 21 day 30 mg/kg 30 mg/kg 60 mg/kg 0.01 mg/kg 1 mg/kg 10 mg/kg 30 mg/kg 10 mg/kg 30 mg/kg Bleomycin l ol i- ody one aily nib aily ns ns ns ns Statistical significance# to 21d bleomycin Every 4 d Every 2 d** Da (sta	Naïve 21 day 30 mg/kg 30 mg/kg 60 mg/kg 0.01 mg/kg 1 mg/kg 10 mg/kg 30 mg/kg 10 mg/kg 30 mg/kg Bleomycin l ol i- ody one aily nib aily ns ns ns ns Statistical significance# to 21d bleomycin Every 4 d Every 2 d** Da (sta	Naïve 21 day 30 mg/kg 30 mg/kg 60 mg/kg 0.01 mg/kg 1 mg/kg 10 mg/kg 30 mg/kg 10 mg/kg 30 mg/kg Bleomycin l ol i- ody one aily nib aily ns ns ns ns Statistical significance# to 21d bleomycin Every 4 d Every 2 d** Da (sta	Naïve 21 day 30 mg/kg 30 mg/kg 60 mg/kg 0.01 mg/kg 1 mg/kg 10 mg/kg 30 mg/kg 10 mg/kg 30 mg/kg Bleomycin l ol i- ody one aily nib aily ns ns ns ns Statistical significance# to 21d bleomycin Every 4 d Every 2 d** Da (sta	Naïve 21 day 30 mg/kg 30 mg/kg 60 mg/kg 0.01 mg/kg 1 mg/kg 10 mg/kg 30 mg/kg 10 mg/kg 30 mg/kg Bleomycin l ol i- ody one aily nib aily ns ns ns ns Statistical significance# to 21d bleomycin Every 4 d Every 2 d** Da (sta
	aone	Contr b	Pirfenid d	Ninteda d	AD-214 ays ays

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• 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

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Statistical significance assessed using ANOVA and post-hoc Dunnett’s test; ns (not significant) = p >0.05, * = p<0.05, ** = p < 0.01
28 relative to 21-day bleomycin vehicle; negative control is an i-body that does not bind specifically to CXCR4; error bars are standard error
of the mean
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NHP GLP toxicology: AD-214 safe

3 non-human primate studies completed

Good Laboratory Practice (GLP) study to evaluate safety and toxicology

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

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

• § body weight § electrocardiography § coagulation § macroscopic and microscopic

• § ophthalmoscopy § respiratory function § urinalysis findings

• § blood pressure § neurological § organ weight function

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

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

Tox study 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 suggestion of off-target toxicities

29

Non-human primate GLP toxicology: Phase I dose justification

Pharmacokinetics

• Elimination half-life 22-29h

• Human equivalent: ~71h (estimate)

• AD-214 available for >3 days

Pharmacodynamics

• 60% receptor occupancy* for 72h at >30mg/kg

• Human equivalent: ~10mg/kg (estimate)

• High receptor binding for >3 days

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Day 1 Male
mg/kg
mg/kg
mg/kg
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Receptor Occupancy - All animals Vehicle
120 10 mg/kg
30 mg/kg
100 100 mg/kg
80
60
40
20
0
-20
Pre-Dose 2 hours 48 hours 72 hours Pre-Dose 2 hours 48 hours 72 hours
post-SOI post-SOI post-SOI post-SOI post-SOI post-SOI
Day 1 Day 25
Percent receptor occupancy
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Supportive of human therapeutic dose window including 10mg/kg intravenously, weekly or every second week

• On peripheral blood mononuclear cells (white blood cells)

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Source: GLP NHP Toxicology Report; external expert pharmacological modelling; error bars are standard deviations (n=6-10 animals per group)

AD-214 Phase I Part A design detail*

Protocol: A Phase I dose-escalating study of the safety, tolerability, PK and PD of single and repeat doses of AD-214 in healthy volunteers (HVs) and patients with interstitial lung disease (ILD)

Part A: Single ascending dose in healthy volunteers Patient numbers by cohort Total n=42 (31 active, 11 placebo, blinded)

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20 mg/kg
10 mg/kg
5 mg/kg
1 mg/kg
0.5 mg/kg
0.02 mg/kg
0.01 mg/kg Active Placebo
0 1 2 3 4 5 6
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Objectives

Primary

• Safety, tolerability of AD-214

• ⁃ adverse events, physical examinations, vital signs, ECG

• ⁃ clinical laboratory tests (hematology, chemistry, coagulation, cytokines)

Secondary

• PK, RO of AD-214

• Immunogenicity of AD-214

Exploratory

• PD markers (SDF-1, CD34+)

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• https://clinicaltrials.gov/ct2/show/NCT04415671?term=adalta&draw=2&rank=1

AD-214 pharmacokinetics increase proportionally with dose

Observed in NHP GLP toxicology study

• Maximum exposure, Cmax, increases in a dose

• proportional manner

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Observed in Phase I HV SAD

• Maximum exposure, Cmax, increases in a dose

• proportional manner

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• Total exposure, AUC0-inf, increases in a more than dose

• proportional manner

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• Total exposure, AUC0-inf, increases in a more than dose

• proportional manner

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• Elimination half-life t1/2 22-29 h

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• Elimination half-life t1/2 = 44±15 h

AD-214 plasma concentrations (log and linear scale)

Maximum and total plasma exposure

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450
1,000.00 400 600 3000
350 Cmax (ug/mL)
300 500 AUC0-inf (hug/mL) 2500
100.00 250
Linear (Cmax (ug/mL))
200
150 400 Poly. (AUC0-inf (hug/mL)) 2000
10.00 100
50
0 300 1500
0 15 30 45 60 75
1.00 Time from start of infusion (h)
200 1000
0.10 0.1 mg/kg 100 500
1 mg/kg
0.01 5 mg/kg 0 0
0 15 30 45 60 75 10 mg/kg 0 5 10 15 20
Time from start of infusion (h) 20 mg/kg Dose (mg/kg)
(ug/mL)
AD-214 plasma concentration
(hug/mL)
Total AD-214 exposure AUC0-inf
Peak AD-214 exposure Cmax (ug/mL)
AD-214 plasma concentration (ug/mL)
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Transient increase in SDF-1 (natural ligand of CXCR4) consistent with CXCR4 engagement

Expected from literature and prior studies

Observed in Phase I HV SAD*

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• Transient increases in SDF-1 levels in response to

• CXCR4 blockade, high participant to participant variability

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• Transient increases in SDF-1 levels at 4 hours in

• some participants, returning to baseline at 24h consistent with CXCR4 blockade

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SDF-1 levels
7,000 Placebo
0.01mg/kg
6,000
0.02mg/kg
5,000 0.1mg/kg
1.0mg/kg
4,000
5.0mg/kg
10mg/kg
3,000
20mg/kg
2,000
1,000
0
0 50 100
Time after start of infusion (h)
SDF-1 plasma concentratrion (pg/mL)
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SDF-1
10000
8000
6000
4000
2000
0
Placebo0.1mg/kg1.0mg/kg5.0mg/kg10mg/kg20mg/kg
SDF-1 plasma concen tration (pg/mL)
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33 * Based on unblinded data, includes only participants for whom pharmacokinetic Cmax was determined
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A clinician’s perspective on AD-214 results so far

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Un-met need in IPF/ILD remains: need to progress new therapies

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Research at The Alfred suggests if targeting CXCR4 works in IPF it may work in other ILD’s

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• AD-214 is well tolerated and ready to move forward into multi-dose studies in healthy

• volunteers and patients

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The data is supportive of extending dosing interval to two weekly at least

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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

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Key insights anticipated from multidose and early patient studies (in addition to safety):

• CXCR4 receptor engagement in tissue

• Nature of the anti-drug antibodies that are expected with a biologic

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

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Prof Glen Westall, leading respiratory and lung fibrosis specialist AdAlta Investor Briefing, 10 March 2021

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Pipeline: diverse target capability supports internal and external pipeline assets

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i-body platform capability Commercial validation
GPCRs
Chemokine
• i-body libraries, IP • Target
Brings
>20 targets to
•
Other which i-body Lysophos- • Discovery, Does Pre-clinical, clinical
binders have pholipid validation development
Enzymes been found
Protein binding
interfaces Neurotensin
Ligand binding sites • Milestones Receives • Binder IP
Acetylcholine • Research fees • Commercialisation
Prostanoid • Royalties rights
Ion channel
Successfully progressed to Stage 4 (lead
optimization) following 10 month discovery program
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Internal pipeline asset creation

• G-protein coupled receptors

• • Fibrosis, inflammation, oncology

External pipeline asset creation

• Multiple co-development partnerships

• New target biology, non-dilutive funding

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• Includes both i-body and VNAR/IgNAR formats

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

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C
Accelerate
(from ~mid-2021)
B
Expand
A
(~mid 2020 to late 2021)
Maximise catalysts from
current funded base (2020)
$8m
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From …

Via …

Towards 2023 …

• i-body platform in clinic for difficult drug targets

• Laying the foundations for growth

• Multi-product, multi-partner platform company

• Clinical and commercial validation: AD-214 Phase I trial and GE partnership

• Progress AD-214

• Build internal and external pipeline

• Continuous platform improvement

• AD-214 partnering, new indications

• ~5 internal GPCR programs

• 3-5 co-development partnerships

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Strategic progress: year to March 2021

Strategic priorities March 2020

March 2021 status

Create value inflections for lead asset AD-214

• Phase I clinical program started: top-line single dose results today

• • Pre-IND meeting and Orphan Drug Designation secured from FDA

• • Pre-clinical data in kidney fibrosis; studies in eye, cancer underway

• • On track to confirm next two indications for AD-214 • Partnering pipeline developing well

• Add 2 assets to internal • Developed selection process •

• pipeline in our “sweet spot” Screened existing targets, now extending to other GPCRs* • On track to commence discovery research on two targets in H2 2021

• Add to external pipeline • GEHC progressed to lead optimisation •

• through a new partnership Co-development partnering pipeline developing well • On track to execute second collaboration by mid 2021

Continuous i-body platform • and AD-214 product Encouraging progress made on i-body2.0, manufacturing and high improvement throughput discovery methods

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Market benchmarks: reaching for the stars!

Fibrosis pipelines	Jul-19 license by Boehringer Ingelheim €45m + €1.1b	Nov-19 acquired by Roche $390m + $1b – Phase II Aug-15 BMS option to buy	Jan-20 platform license by Boehringer Ingelheim $?m + $1b milestones
	Phase I	$150m + $1.25b milestones	Preclinical
Micro- antibody platforms	April-16 license by Abbvie $40m upfront + $645m milestones & royalties	Feb-18 collaboration with Seattle Genetics (3 targets) $30m upfront + $1.2b milestones & royalties	Feb-18 acquired by Sanofi €3.9b
GPCR platforms	Feb-15 acquired by Sosei $400m Phase Ib asset + 7 pre-	Jul-15 acquired by Celgene $7.8b Ph III, Ph II and GPCR	April-16 license with Boehringer €8m + €125m milestones
	clinical leads	platform	Phase I GPCR nanobody

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