ENTROPY NEURODYNAMICS LIMITED — Investor Presentation 2021

Aug 19, 2021

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ASX ANNOUNCEMENT

Investor Webinar Presentation

20 August 2021, Melbourne, Australia: Exopharm Limited (ASX:EX1) is pleased to announce its participation in the ShareCafe Small Cap "Hidden Gems" Webinar, to be held Friday 20[th] of August 2021 from 12:30pm AEST / 10:30am AWST.

Deputy CEO and Chief Commercial Officer, Dr Chris Baldwin will provide an overview of the Company and its exome nanoparticle and nucleic acid cargo technology which has a number of advantages for the delivery of nucleic acid cargos (such as the particles delivered in mRNA vaccines).

This webinar can be viewed live via Zoom and will provide viewers the opportunity to hear from and engage with a range of ASX-listed leading micro/mid cap companies.

To access further details of the event and to register at no cost, please copy and paste the following link into your internet browser:

https://us02web.zoom.us/webinar/register/5416151767246/WN_8mZL8zwVSaqS1IuuVcTmtw

A recorded copy of the webinar will be made available following the event.

A copy of the investor presentation to be delivered during the webinar is attached.

By the Board - this announcement has been authorised for release by the board.

Company and Media Enquiries:

Join our mailing list to receive updates: mailto:info@exopharm.comhttp://exo.ph/ExoMails www.exopharm.com P: +61 (0)3 9111 0026

Rudi Michelson

Monsoon Communications Tel: +61 (0)3 9620 3333

EXOPHARM LIMITED ACN: 163 765 991 ASX:EX1 Address: Suite 201, 697 Burke Road Camberwell 3124 Email: info@exopharm.com Web: www.exopharm.com

ABOUT EXOPHARM

Exopharm (ASX:EX1) is a clinical-stage biopharmaceutical company using exosomes to deliver a new class of transformative medicines and generate revenue from multiple partnership deals.

Exosomes are seen by the Biopharma industry as a highly differentiated platform with the potential to enhance tissue delivery for a variety of payloads like mRNA and proteins – part of the global market for drug delivery systems which is growing at a compound annual growth rate (CAGR) of 5% and valued at around US$170 billion in 2021.

For some medicines, exosomes are an alternative and superior means for delivery inside the body, alongside technologies such as lipid nanoparticles (LNP), cell penetrating peptides, viral vectors and liposomes.

Exopharm’s LEAP technology solves the challenge of purifying clinical-grade exosomes at large scale and low cost.

Exopharm also has two exclusive proprietary technologies that allow advanced customisation of exosomes – the LOAD technology improves loading of nucleic medicines into exosomes and the EVPS technology allows exosomes to be directed towards selected cell types.

Exopharm uses variations and combinations of LOAD and EVPS to enable its Biopharma partners to improve delivery of their drug candidates and help them design and test new exosome medicines aimed at treating a wide scope of medical problems including neurological disease, infectious disease, cancer, and fibrosis.

FORWARD LOOKING STATEMENTS

This announcement contains forward-looking statements which incorporate an element of uncertainty or risk, such as ‘intends’, ‘may’, ‘could’, ‘believes’, ‘estimates’, ‘targets’, ‘aims’, ‘plans’ or ‘expects’. These statements are based on an evaluation of current corporate estimates, economic and operating conditions, as well as assumptions regarding future events. These events are, as at the date of this announcement, expected to take place, but there cannot be any guarantee that such events will occur as anticipated or at all given that many of the events are outside of Exopharm’s control or subject to the success of the Development Program. Furthermore, the Company is subject to several risks as disclosed in the Prospectus dated 6 November 2018.

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Exopharm Ltd Delivering Transformative Medicines

August 2021

1.0

IMPORTANT INFORMATION

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Purpose of presentation: This presentation (including this document, any related video or oral presentation, any question and answer session and any written or oral material discussed or distributed in relation to this presentation) has been prepared by Exopharm Limited (ACN 163 765 991) (Exopharm or Company). This presentation is intended for sophisticated or professional investors (as those terms are defined in the Corporations Act 2001 (Cth)), and their professional investment advisors and has been prepared for the sole purpose of providing general high-level information on Exopharm and its operations.

Not an offer or solicitation: This presentation is not investment advice nor an offer to subscribe for securities or otherwise invest in Exopharm, and it should not be relied upon to make any investment decision.

Nature of presentation: This presentation is not a prospectus, product disclosure statement or other investment disclosure document, and the level of disclosure in this presentation is less than such disclosure documents. This presentation does not purport to contain all of the information that a prospective investor may require to make an evaluation of Exopharm or its business activities and nothing in this presentation is, or is intended to be, a recommendation to invest in Exopharm. Exopharm does not purport to give financial or investment advice. No account has been taken of the objectives, financial situation or needs of any recipient of this presentation.

Forward-looking statements: This presentation may contain forward-looking statements which may be predictive in nature and incorporate an element of uncertainty or risk, such as ‘intends’, ‘may’, ‘could’, ‘believes’, ‘estimates’, ‘targets’ or ‘expects’. These statements are based on an evaluation of current economic and operating conditions, as well as assumptions regarding future events. These events are, as at the date of this presentation, expected to take place, but there cannot be any guarantee that such will occur as anticipated, or at all, given that many of the events are outside Exopharm’s control. The stated events may differ materially from results ultimately achieved. Accordingly, neither Exopharm nor any of its directors, employees, contractors or advisors make any warranty or assurance that the results, performance or achievements expressed or implied by the forward-looking statements contained in this presentation will actually occur. Further, other than as required by law, Exopharm may not update or revise any forward-looking statement if events subsequently occur or information subsequently becomes available that affects the original forward-looking statement.

Disclaimer: Neither Exopharm nor its officers, employees, contractors or advisors give any warranty or make any representation (express or implied) as to the accuracy, reliability, relevance or completeness of the material contained in this presentation. Nothing contained in this presentation is, or may be relied upon as a promise, representation or warranty, whether as to the past or the future. Except for statutory liability which cannot be excluded, Exopharm, its officers, employees, contractors and advisors expressly disclaim any responsibility for the accuracy or completeness of the material contained in this presentation and exclude all liability whatsoever (including in negligence) for any loss or damage which may be suffered by any person as a consequence of any information in this presentation or any error or omission therefrom.

Professional advice: Recipients of this presentation should consider seeking appropriate professional financial, taxation and legal advice in reviewing the presentation and all other information with respect to Exopharm and evaluating its business, financial performance and operations.

Confidentiality and copyright: While this is a non-confidential presentation, it still provides confidential and commercially sensitive information which is provided for the intended recipient only. Organisations or Persons viewing this presentation must not disclose the presentation or its contents to any third parties other than external consultants of the recipient for the purposes of obtaining a professional review, financial, taxation or legal advice, or as required by law or court order. Exopharm holds the copyright in this paper. Except as permitted under the Copyright Act 1968 (Cth), this paper or any part thereof may not be reproduced without Exopharm’s written permission.

© Exopharm Ltd 2021

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Exopharm Ltd

Overview

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• Australian clinical-stage company at the forefront of developing transformative medicines based upon exosomes (extracellular vesicles, EVs)

• Over 40 staff based in Melbourne and Europe

• Publicly traded on the ASX (ASX:EX1) (listed Dec 2018) 157.1 million shares on issue, current market cap. ~AU71 million

• A platform technology company with application to many exosome medicines – using our exclusive LEAP, LOAD and EVPS technologies

Priorities

• Leading the emerging exosome field through our exosome technologies and exosome medicines

• Making exosome technologies available to established biopharmaceutical companies to empower the processes underpinning exosome manufacture

• Delivering existing and emerging drug candidates through precision exosome medicines

Exosomes: Nature’s Solution to Delivery in the Body

Exosomes (also referred to as extracellular vesicles or EVs) are natural, multifunctional and stable nanoparticles that transfer cargo and messages between cells.

1. PACKAGE LIPID BILAYER

Natural exosomes can be produced from cells in a bioprocessing facility.

2. ADDRESS PROTEINS

Outer membrane that forms the 1. PACKAGE exosome (same membrane as human cells)

3. CARGO

• RNA, PROTEINS, & LIPIDS

External proteins that improve 2. ADDRESS targeting of exosomes to specific cell types

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The materials delivered by exosomes, 3. CARGO including instructions (RNA) and building materials (lipids, enzymes, proteins)

© Exopharm Ltd 2021

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Uncovered by Scientists in 2007, in 2021 Exosomes are Emerging as a New Frontier in Medicines Delivery

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Exosomes represent a dynamically growing segment in life sciences with opportunities in research, diagnostics and therapeutic applications.

Dr Uwe Gottschalk, Chief Technology Officer for Lonza (2017)

Targeted and nontargeted exosomes offer a highly differentiated platform with the potential to enhance tissue delivery for a variety of payloads like mRNA and proteins.

Dr Madhu Natarajan, Head of the Rare Diseases Drug Discovery Unit at Takeda (2020)

Now is the time for researchers to usher in a new era of therapeutic possibilities using RNA-delivering, natural exosome vesicles.

Professor Phillip Askenase MD, Yale University School of Medicine (2020)

Exopharm is at the forefront of exosome medicines

© Exopharm Ltd 2021

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From Platform to Products, Exopharm’s EV Medicine Strategy

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Establish EV
Technology
Platform
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Design economical, scalable, and consistent processes for EV medicines from Day 1 Once established, leverage to drive EV medicines globally

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Produce EVs from high-confidence sources (platelets, MSCs) for early human safety trials to credential manufacturing processes

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Customize EVs for cell-type specific delivery of precision medicines including nucleic acids and proteins

Engineered EV

© 2021 Exopharm Ltd. 6

Three Unique & Powerful Technologies Underpin our Partnering and Exosome Medicines

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Scalable, economical GMP process for purifying exosomes

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Tropism-conferring approach for engineering exosome surface proteins

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Activity enhancing method for delivering RNA by exosomes

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EVPS US patent is granted, LOAD patent is progressing and LEAP patent is granted in Russia and progressing through national phase in USA under fast-track process.

© 2021 Exopharm Ltd. 7

Exopharm Has the Only Known Technology for Commercial-scale Exosome Medicine Purification

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State of the Art, Exosome Purification as of June 2020*

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Unlike all alternatives, LEAP
AF4 technology:
Research Scale
Nano-FCM
UC
Immunoaffinity 1. Uses industry-standard
Diagnostic Scale
Commercial reagents equipment/processes
Microfluidics Phase I Scale 2. Uses low-cost, reusable
consumables
Density gradient
Phase II/III Scale 3. Scales economically beyond
thousands of doses
SEC
4. Is proprietary (i.e. patent
Commercial
Filtration applied for)
Manufacturing
Scale
LEAP unlocks the potential
Low of Exosome Medicines
SCALABILITY High
High
COST
Low
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• ** LEAP assessment from Exopharm, based on industrial use to date; LEAP Patents processing through National phases at present.

• Adapted from https://doi.org/10.1016/j.tibtech.2020.05.012

© Exopharm Ltd 2021

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SARS-CoV-2 RNA Vaccines Use “Artificial Exosomes”

Pfizer and Moderna SARS-2 vaccines package RNA into artificial synthetic lipid nanoparticles (LNPs) However, LNPs have major limitations for drug delivery: • Toxicity

• Anti-LNP immune response

• • Inefficient cellular delivery

Naturally occurring exosomes from human cells have evolved an optimal composition over billions of years and have none of these limitations .

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Solid lipid nanoparticle

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LNP
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DOI: 10.3389/fmolb.2020.587997

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Webinar: Overcoming the Delivery Challenge for Nucleic Acid Drugs

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26 August 2021 10 – 10:30 am AEST

Presenters

Dr Jennifer King King BioConsulting RNA Medicines and Delivery: The Importance for the Future of Medicine

Dr Anna Cifuentes-Rius Monash University

Delivery by LNPs and Exosomes: When They Are Useful and Why

LEAP Exosomes Overcome Significant Issues Associated with LNP Delivery

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	Lipid Nanoparticles	Exosomes
Targeting	Yes	Yes
Stability	Yes	Yes
Efficient Uptake	No	Yes
Non-toxic	No	Yes
Frequent dosing	No	Yes
Scalability without LEAP (Manufacture/ Purification)	Yes	No
Scalability with Exopharm’s LEAP Technology		YES

© 2021 Exopharm Ltd. 11

EVPS Construct

Cargo : Cytoplasmic domain for reporter proteins (or anti-viral) carried as cargo

VSVg : Transmembrane domain passes through cell and exosome bilipid layers

CTD Cell-targeting domain Cytoplasmic domain

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CTD : Cell-targeting domain, a protein used by to enter cells (such as a viral coat protein, nanobody, cell-penetrating peptide, etc)

Note: VSVg = vesicular stomatitis virus glycoprotein

Exosome from EVPS modified producer cell

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© 2021 Exopharm Ltd. 12

Confocal Imaging of Stable Spike-RFP Stable Cell line

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RFP
DAPI RFP
RFP
everywhere
within the
cell
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Merge
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RFP control vector

RFP COV2 Spike RFP 'Membranelocalized’ RFP expression

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Merge
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CoV-S EVPS Construct # 3R

© 2021 Exopharm Ltd. 13

EVPS Technology Proven with Large Targeting Moieties

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180
Cargo
160
mVSVg
140
(transmembrane)
Targeting protein
120
100
Nanobody
80
60 CPP
mCherry GFP
40
20
0
Cargo Targeting
SARS-2 Spike Protein
Cognevo X
ScFv
RFP RFP
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Using EVPS construct, very large proteins can expressed by stable producer cell lines. Technology can be applied to wide range of targeting proteins and/or large protein cargoes

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© 2021 Exopharm Ltd. 14

LOAD Localizes RNA into EVs

Standard approach

siRNA evenly across the cytoplasm

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Producer cells electroporated with siRNA

Nuclei EVs (cd63)

siRNA Merge

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Producer cells electroporated with LOAD powered siRNA

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LOAD technology enriches RNAi near EV biogenesis sites Therapeutic effect/cost of delivery improve substantially using LOAD technology

siRNA is localized within EVs; enrichment factor of 10 – 100x

© 2021 Exopharm Ltd. 15

Together these Technologies Create a Precision Medicine Factory

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Rare diseases
Cancers
Viruses
Neurological
diseases
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© 2021 Exopharm Ltd. 16

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Right Place, Right Time, Right People

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© Exopharm Ltd 2021

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Thank you

Exopharm Ltd (ASX:EX1)

Chris Baldwin Deputy CEO/Chief Commercial Officer +61 450 290 280 chris.baldwin@exopharm.com www.exopharm.com

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