VECTUS BIOSYSTEMS LIMITED — AGM Information 2023

Nov 21, 2023

ABN 54 117 526 137

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Vectus Biosystems Limited

Chairman’s Address to the 22 November 2023 Annual General Meeting

The 2023 year was very productive and Vectus achieved a significant number of milestones, commencing with the September 2022 finalisation of the Phase Ia human safety clinical trial in collaboration with the Nucleus Network in Melbourne and Syneos Health. The Company’s lead cardiovascular candidate, VB0004, is supported by a broad portfolio of issued patents. Vectus’ strategy is to develop and perform early validation of its drug candidates to the point where they become commercially attractive to potential pharmaceutical partners. Vectus continues with progress in its Phase Ib human trials of VB0004 that addresses a significant unmet need for anti-fibrotic agents for patients with cardiovascular and/or kidney disease.

In September 2022 Vectus announced to the market that it had completed all protocol requirements of both the Single Ascending Dose (S.A.D.) and the Multiple Ascending Dose (M.A.D.) segments of its first-in-human trial. The Trial Safety Committee reviewed data from all five planned S.A.D. cohorts as well as all three planned M.A.D. cohorts. The Phase Ia trial established an impressive safety profile for VB0004, with a maximum tolerated single dose of 300mg and no significant adverse events seen in the M.A.D. studies at 10mg, 30mg or 100mg administered daily over a 14-day period. Also established are consistent pharmacokinetics of six-to-eight hours to achieve maximal plasma concentration and a half life in excess of 10 hours. The completion of the Phase Ia trial is a significant milestone in proving the safety of the Company’s antifibrotic / antihypertensive drug, and is particularly pleasing as Vectus moves towards the next phase of testing of a compound that can have a significant and widespread, global positive impact on disease, the pathology of which has many aetiologies. While there were challenges in recruiting patients for the Phase Ia trial due to COVID-19, the results achieved made the wait worthwhile.

Vectus continues to advance work on its library of over 1,000 compounds, derived from the platform underpinning VB0004. Vectus has selected additional emerging leads to address liver fibrosis (VB4A32) and lung fibrosis (VB4-A79) more specifically. The Company’s drug candidates have the potential to attract first-in-class status and therefore the potential for higher levels of re-imbursement on the basis of being innovator compounds that address unmet needs. Vectus’ drugs are targeting some of the largest pharmaceutical franchises in the world. Fibrotic diseases can account for up to 40% of the world’s current mortality rate. The Company’s initial human clinical trial targeted the validation of safety and tolerance. Further studies are examining the efficacy of VB0004 to treat various conditions that cause damage in the cardiovascular system. Vectus continues its research into the possible opportunity to target the fibrotic damage resulting, in some cases, from COVID-19. VB0004 has the potential for its orally-active small molecules to play a role in this unmet need.

I see in my work as a Radiologist and Clinical Physician, the real need for this new class of drugs, providing significant social, patient and health economic outcomes. Fibrosis, or scar tissue, is the end point of a whole host of diseases, including high blood pressure, injury, post infections (such as COVID19), radiotherapy and silicosis. To have potential drugs, like those in the Company’s stable, that can not only stop the growth of scar tissue, but also reverse the fibrosis, is a major development in medicine. To take the drug orally, in tablet form, also decreases the cost of production and, more importantly, increases the ease of use by patients. The use of Vectus’ compounds to reduce blood pressure is also very significant.

VECTUS BIOSYSTEMS LIMITED ABN 54 117 526 137

3-11 Primrose Avenue, Rosebery, NSW 2018 Telephone: +61 2 9662 4144 Facsimile: +61 2 9697 0933 Website: www.vectusbiosystems.com.au

ABN 54 117 526 137

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Finance

The funds expended by the Company during the last year were largely in connection with the finalisation of the Phase Ia and the Phase Ib human clinical trials for VB0004. Cash-on-hand at 30 September 2023 was $1,769,000. In addition, Vectus received a $1,226,161 R&D refund on 20 November 2023 from the Australian Taxation office. The Company continues to evaluate a number of options to address its future capital requirements, and the funding of its future R&D, and product commercialisation programme. Vectus remains in active dialogue with potential investors, and a number of brokers and providers of other sources of funding, and is in strategic discussions with potential trade partners.

Commercialisation Process

Since the successful completion of the Phase Ia human trial, and during the Phase Ib human trial, the Company is increasing its dialogue with some of the world’s leading pharmaceutical companies and regional mid-sized firms, and feedback has been positive. Vectus’ strategy is to develop and perform early validation of its drug candidates to the point where they will become commercially attractive to potential pharmaceutical partners. The Company’s objective is then to partner with one or more companies via a licencing programme, focusing initially on VB0004. The additional compounds also present an attractive commercial opportunity for Vectus and clinical success in any one of the Company’s compounds is likely to generate increased interest by pharmaceutical companies. Today there is a rapidly evolving interest in the franchises and disease states that Vectus addresses. Particularly in Asia, liver fibrosis represents an important market because of the significance of hepatitis in this region. Whilst new drugs have become available to deal with this viral infection, they do not reverse existing damage and, in many cases, the fibrosis can be progressive. The Company’s compound ideally complements these new drugs by potentially arresting progression and reversing damage in a clinically-significant way. This represents, both socially and financially, a very large unmet need, and could be a transformational therapy of great significance.

Accugen

Since the 2022 AGM significant advancements have been made to enhance the Accugen technology aimed at improving the speed and accuracy of measuring the amount of DNA and RNA in samples tested in laboratories. The technology, consisting of AccuCal™ and RealCount™ software, offers a time, cost and accuracy benefit compared with currently available systems. This novel and wellpatented platform is 100% owned by the Company. Vectus’ Accugen platform has been instrumental in the development of the Company’s lead compounds and library. The technology comprises reagents and software that quantitate polymerase chain reactions (qPCR). Activities in the commercialisation programme continue in relation to the introduction of Accugen’s consumables and software into the qPCR market. This work aims to tap the broad potential market for the Accugen product and may lead to a combination of direct sales, distribution partnerships and licensing opportunities, including applications related to large and growing market of food safety.

The Vectus Team

The Board’s sincere gratitude goes to Dr Karen Duggan and the Vectus team, for their work during the past year in moving VB0004 through the important Phase Ia human trials and into the Phase Ib human trials. Thank you for the efforts and guidance from the Board members in working towards success and growth for the Company. Vectus’ shareholders have been active in their support during this exciting phase of the Company’s development. We look forward to progressing our activities and growth of the Company’s unique library of assets with the objective of contributing in a meaningful way to society, patients, our stakeholders and the delivery of improved healthcare worldwide.

Vectus Biosystems Limited

Ron Shnier

Chairman

The AGM Presentations have been authorised for release by the Board.

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AGM 2023

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Solutions for unmet medical needs
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Protein Deposition Diseases

Three groups:

• Fibrosis related diseases

Accumulated proteins collagen and fibronectin

Common diseases, major unmet needs, fibrosis is the pathology underlying Heart failure

Kidney failure Liver cirrhosis and failure Pulmonary fibrosis

Accounts for more than 40% of all deaths

• Amyloidoses

Accumulated proteins vary by organ, mostly rare diseases

Brain‐ amyloid beta (Aβ) => Alzheimers

Heart – transthyretin (TTR) => cardiac amyloidosis, ATTR‐CM Kidney – TTR => renal amyloidosis

Intestine – amyloid A (AA), β2 microglobulin, prealbumin Pancreas – Islet amyloid polypeptide (IAPP)

Mostly rare diseases

• Mixed Fibrosis and Amyloid Deposition

Accumulated proteins AA, AL or TTR plus collagen, fibronectin Heart

Kidney Pancreas

VB0004 & CARDIAC FIBROSIS

VB0004 has been shown to:

• Rescue cardiac tissue damaged by fibrosis

• Repair existing cardiac damage

14‐Week Control

Fibrous tissue (blue staining) is visible around blood vessels and extending between muscle fibres

• i.e. VB0004 is transformational

Treatment with VB0004 at 3 Doses

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At the highest dose (500pmol/kg/min), VB0004 reversed pre‐existing fibrosis, while a dose response effect on the level of fibrosis is apparent

5% Ethanol 18‐Week Control (Vehicle Control For VB0004) Fibrosis visible as blue stained tissue is present throughout the section

Heart At 18 Weeks After 4‐week Treatment with VB0004 (500 Pmol/Kg/Min)

Minimal fibrosis is visible; normal architecture has been restored

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VB0004 & KIDNEY FIBROSIS

In the kidney VB0004 has been shown to:

• Reverse renal interstitial fibrosis at all doses

• Restore normal architecture at all doses

14‐Week Control

Fibrosis (blue) partially surrounds some but not all tubukes

• (i.e. VB0004 is considered transformational)

Treatment with VB0004 at 3 Doses

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5% Ethanol 18‐Week Control (Vehicle Control For VB0004) Fibrosis has progressed to surround most tubules

Kidney At 18 Weeks After 4‐week Treatment with VB0004 (500 Pmol/Kg/Min) No fibrosis visible

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Benchmarks

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25 15 25
20 J F 20
J 10
15 15 F
J
R2=0.9896
10 10
5
F VIP Enalapril B
5 5
0 0 0
1 10 100 1000 1 10 100 1000 1 10 100 1000
VB0004 (pmol/kg/min) Dose (pmol/kg/min) Dose (pmol/kg/min)
VB0004 VIP
VB0004
VB0004
VIP
R2=0.9682
Enalapril
D elta SB P (m m H g)
Enalapril
R2=0.9640
D elta C ard iac Fib ro sis (% su rface area) D elta R enal Fib rosis (% surface area)
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In these experiments enalapril was dose adjusted to provide the same reduction in SBP as VIP (5pmol/kg/min, blue). The dose of enalapril required was 705 pmol/kg/min (red). As can be seen in the above diagrams VB0004 at lower doses achieved greater reductions in SBP than enalapril (left). VIP (5pmol/kg/min) was superior to VB0004 at all doses in decreasing fibrosis in heart (centre) but was only better than the lowest dose of VB0004 (10 pmol/kg/min) in reducing renal fibrosis (right). In both heart and kidney VB0004 achieved much greater reductions in fibrosis at markedly lower doses than enalapril.

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VB0004 – Fibrotic Mediators & CK Activity

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2500 100
B
2000 80
VB0004 reduced B
VB0004 treatment reduced: B
1500 plasma CK activity in a 60
1000 p<0.0005 dose related manner 40
500 20
Ang II synthesis
0 0
(decreased Agt expression) EtOH Control 18 Weeks VB0004 18 Weeks 1 10 100 1000
VB0004 Dose (pmol/kg/min)
1500 120
100
1000 p<0.01 Plasma CK activity B
B
was linearly related 80 B
500 B
fibrotic mediator expression to blood pressure 60
R [2] =0.96234
0 40
EtOH Control 18 Weeks VIB0004 18 Weeks 190 200 210 220 230
AT1a Systolic Blood Pressure (mmHg)
1500
TNFα 120
Plasma CK activity 100
1000 p<0.01 B
was linearly related B
80
B
500 to cardiac fibrosis B
60
R [2] =0.98581
0 EtOH Control 18 Weeks VIB0004 18 Weeks 40 0 5 10 15 20
Myocardial Fibrosis (percent surface area)
6
Plasm a Creatine Kinase (u/L) R2=0.99924
Agt Expression (Replicates/ng RNA)
Plasma Creatine Kinase (IU/L)
AT1a Expression (Replicates/ng RNA)
Plasma Creatine Kinase (U/L)
AT1a Expression (Replicates/ng RNA)
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VB0004 & PULMONARY FIBROSIS

In the lung:

• VB0004 reversed fibrosis present 2 weeks after treatment with bleomycin (an anticancer drug)

• (i.e. VB0004 also transformational in the lung)

16‐Week Control Increased fibrosis (cyano), reduced capillaries (red dots)

Treatment with VB0004

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30
20 #

10
0
Control 16 VB0004 Control 20
Pulmonary Fibrosis (%surface area)
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20‐Week Control Increasing fibrosis, decreasing capillaries VB0004 at 20 weeks Fibrosis removed capillaries reconstituted

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Treatment with VB0004

• Reduced profibrotic mediator expression

• Reduced Ang II synthesis

• Reduced CK activity (potential biomarker)

• Reduced SBP

• Removed accumulated protein in heart, lung and kidney (i.e. reversed established fibrosis)

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Removal of established accumulated proteins can be accomplished by

• Activating macrophages which then remove the protein

• Making protein fibrils more susceptible to protease digestion

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Removal of Accumulated Proteins

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0
-0.1

-0.2

-0.3 VB0004
Baseline Normalised Cell Index
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25
20
J
J
15
B
J
B
10
B
5
-0.2 -0.1 0
Baseline Normalised Cell Index
Fibrosis (% surface area)
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Reversal of fibrosis in heart and kidney implies VB0004 stimulates/activates macrophages. To test this hypothesis RAW264 cells (a mouse macrophage cell line) were incubated with increasing concentrations of VB0004 in the xCELLigence RTCA, the graph above shows an increasing response with increasing concentration of VB0004 indicating a macrophage response to VB0004

Relationship between cellular impedance changes in RAW 264 cells and fibrosis in heart (blue R2=0.9898) and kidney (red R2=0.9873). The strong correlations suggest that macrophages typified by RAW 264 participate in the proteolytic activity required to restore normal tissue architecture which occurred with VB0004 treatment

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INTELLECTUAL PROPERTY

VB0004 PATENT COVERS

• Compositions of matter

• Methods of use

• Priority date September 2014

VB0004 AND LUNG FIBROSIS

• Methods of use

• Priority date July 2017

• Expiry 2037 (+5 years on FDA/EMA approval)

• Expiry 2034 (+5 years on FDA/EMA approval)

VB0004 PATENT GRANTED IN ALL MAJOR JURISDICTIONS

VB0004 METHOD OF SYNTHESIS PATENT

• Priority date March 2017

• USA, Europe, Japan, Peoples Republic of China, Republic of South Korea, Russian Federation

• As well as Australia, Israel, Philippines, South Africa, Canada, ARIPO

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Towards the Clinic

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SYNTHESIS AT SCALE & COST

FIRST GMP SYNTHESIS BY GLYCOSYN

SECOND GMP SYNTHESEIS ASSYCHEM

• Yield increased as scale increased

• VB0004 manufactured to 5kg scale

• Cost efficient at 5kg scale < $(US)0.05

• per mg

• Estimated dose 1‐5mg

• Stability studies – stable at 2 yrs (long shelf‐life)

• Campaign planned to provide 3 validation batches

• Confirm consistency of the synthesis process

• Samples of all 3 batches will undergo 4 yr stability testing

• Meets FDA requirements for GMP manufacture for Phase 1 and 2 clinical trials

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DEMONSTRATED SAFETY (extensive IND Toxicology)

SAD AND MAD (2 SPECIES)

• Single Ascending Dose (SAD) to 2,000mg/kg no adverse events

• 7 day Multiple Ascending Dose (MAD) to 2,000mg/kg no adverse events

• 28 day MAD to 500mg/kg/day in dogs 1,000 mg/kg/day in rats no adverse events

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MUTAGENIC
POTENTIAL
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• In vivo and in vitro tests low to no mutagenic potential

CARDIOVASCULAR SAFETY

• hERG studies ‐ low arrhythmia potential

• Dog cardiovascular safety – No effects on cardiovascular function at maximum dose of 10 grams

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METABOLISM
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• Metabolites are the same in human, rat and dog

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RESPIRATORY
SAFETY
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• Rat study no adverse events
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DRUG
INTERACTIONS
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• No Inhibition of major drug metabolising enzymes (drug interactions less likely)

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PHASE 1a

1 5

Outcomes

SAD

All planned doses were completed No VB0004 related AE’s

Maximum tolerated dose 300mg

Metabolised to VB4‐glucuronide undergoes enterohepatic circulation

Tmax occurred between 6 and 8 hrs post dose

T between 10 and 15 hrs 1/2

Plasma concentration decreased by food , Tmax and T1/2 appear unchanged

MAD

All planned doses were completed

No VB0004 related AE’s

Maximum tolerated dose 100mg

Metabolised to VB4‐glucuronide undergoes enterohepatic circulation

Tmax occurred between 6 and 8 hrs post dose T between 10 and 15 hrs 1/2 Repeated dosing did not cause accumulation

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Outcomes – PK Profile

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PHASE 1b

1 8

Aims – Possible Outcomes

demonstrate clinical efficacy of VB0004 (↓BP) demonstrate via selected bio‐markers anti‐fibrotic actions of VB0004 on

• heart

and/or

• kidney

correlate ↓BP with VB0004 plasma concentra�ons correlate changes in selected bio‐markers with plasma VB0004

Currently recruiting

• Fist in class therapeutic

VIP agonist

• Transformational agent

reverses existing disease effective removal of deposited proteins restores normal tissue architecture

effective in multiple organs

• Side effects

none discernible in animals or humans even at very high dose

• Pharmacokinetics

mane dosing with only minimal formulation

• Synthesis

3 steps

cost competitive ($0.05 /mg)

• Stability – exceeds 2 years

• Long patent life –expires 2034

• (+5yrs on FDA/EMA approval i.e. 2039)

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Austrade BIO23 Advance Australia Delegation

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Presentation from Merck (US) outlining their format for engagement. Initial meeting – if interested pharma will ask for non‐confidential deck. Review non‐confidential deck – questions and responses. If wanting to proceed the next steps are for pharma to ask for CDA then a confidential deck.

Review confidential deck – questions and responses. If wanting to proceed he next step is for pharma to ask for a “data room”. If they still wish to proceed a terms sheet, which details the up front payment, milestone payments etc. It was emphasised that the process can be drawn out as pharma deliberates each step.

From our interactions European, Asian and US pharma all follow this format.

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Indicative Deal

Upfront and near term milestones $100m Milestones to licensing $1.2bn

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Regulatory Environment

Addition of fast‐track category Alzheimer’s disease, heart failure kidney failure

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Regulatory Environment

Orphan/fast track status from FDA/ EMA Phase 2a for either Open label Approx 30 subjects Followed by Phase 2b with 300‐400 subjects Apply for FDA/EMA approval

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PATENT PORFOLIO

VIP patents for heart, kidney and aortic fibrosis – granted all jurisdictions

VIP fragment patents compositions and methods of use for hypertension, cardiac, renal and aortic fibrosis

– granted most jurisdictions

VB0004 compositions and methods of use for hypertension, cardiac and renal fibrosis

– granted Russian Federation, Israel, Singapore, ARIPO, Canada, Philippines, South Africa, Ukraine, Vietnam, Nigeria, Mexico, accepted in Indonesia

VB0004 library of approx. 70 related compounds compositions and methods of use for treatment of hypertension, cardiac and renal fibrosis

– granted US, Australia, China, Europe, Japan, Korea, Russia, Ukraine, Hong Kong, Vietnam, Singapore, accepted in South Africa, ARIPO, Brazil, accepted Mexico

VB4-A32 and library of related compounds compositions and methods of use for treatment of hepatic, cardiac and renal fibrosis

– granted US, Europe, Australia, South Africa

VB4-P5 and library of related compounds compositions and methods of use for treatment of renal cell death, renal fibrosis and hepatic fibrosis

– granted US, China, Australia, South Africa, accepted Europe, Japan, Russia, Israel

GMP method of synthesis VB0004 – granted USA, Australia, India, accepted Europe, China

VB4-A79 and related compounds compositions and use for treatment of pulmonary fibrosis – granted Australia, China, accepted USA, Europe, Mexico

VB0001 and related compounds compositions and use for management of hypertension and fibrotic disease

–PCT application

VB0002, VB0003 and VB0005 and related compounds compositions and use for management of hypertension and fibrotic disease

– national phase

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CONTACT

KAREN DUGGAN MD FRACP Chief Executive Officer kduggan@vectusbiosystems.com.au