ENTROPY NEURODYNAMICS LIMITED — Investor Presentation 2021

Jun 29, 2021

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ASX ANNOUNCEMENT

INVESTOR DECK – to be presented at the Stockhead V-Con on Biotechs

30 June 2021

Melbourne, Australia: Exosome medicine company Exopharm Limited (ASX:EX1) advises that it will be presenting the attached Investor Deck at today’s Stockhead V- Con on Biotechs.

This presentation provides updates on the exosome technology and exosome medicines programs at Exopharm.

This announcement has been approved by the Board for release to the ASX.

Company and Media Enquiries:

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

Rudi Michelson Monsoon Communications Tel: +61 (0)3 9620 3333 rudim@monsoon.com.au

EXOPHARM LIMITED ACN: 163 765 991 ASX:EX1 Address: Level 17, 31 Queen Street Melbourne 3000 Telephone: 03 9111 0026 Email: info@exopharm.com Web: www.exopharm.com

ABOUT EXOPHARM

Exopharm (ASX:EX1) is a clinical stage biopharmaceutical company using exosomes (extracellular vesicles (EVs)) from cells to generate a new class of precision medicines and regenerative medicines.

Various Exopharm EV products harness the powerful natural ability of EVs to efficiently target cells and transfer selected materials into cells and across barriers.

Exopharm has two exclusive proprietary technologies that extend the utility of EVs into engineered EV medicines (EEVs): the LOAD technology improves loading of nucleic medicines into EVs, and the EVPS technology allows EVs to be directed towards selected cell types. Exopharm uses combinations of LOAD and EVPS to develop a pipeline of EEV products aimed at treating a wide scope of medical problems including neurological diseases, infectious diseases, cancer, and fibrosis.

Exopharm’s LEAP technology solves the challenge of purifying EVs at large scale. With LEAP, Exopharm is also developing naïve (or natural) EVs (NEVs) from adult stem cells and platelets as regenerative medicine products. NEVs have the potential to deliver the regenerative benefits of cells without the challenges of administering cells to patients. NEV products target a broad range of medical problems including osteoarthritis, autoimmune conditions, acute injury and chronic injury.

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.

INHERENT RISKS OF INVESTMENT IN BIOTECHNOLOGY COMPANIES

There are a number of inherent risks associated with the development of biopharmaceutical products to a marketable stage. The lengthy clinical trial process is designed to assess the safety and efficacy of a drug prior to commercialisation and a significant proportion of drugs fail one or both of these criteria. Other risks include uncertainty of patent protection and proprietary rights, whether patent applications and issued patents will offer adequate protection to enable product development, the obtaining of necessary drug regulatory authority approvals and difficulties caused by the rapid advancements in technology. Companies such as Exopharm are dependent on the success of their research and development projects and on the ability to attract funding to support these activities. Investment in research and development projects cannot be assessed on the same fundamentals as trading and manufacturing enterprises. Therefore, investment in companies specialising in drug development must be regarded as highly speculative. Exopharm strongly recommends that professional investment advice be sought prior to such investments.

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Exopharm Ltd Delivering Transformative Medicines

June 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)

• 40 staff based in Melbourne, Australia; 1 based in Europe

• Publicly traded on the ASX (ASX:EX1) (listed Dec 2018) 157.1 million shares on issue, current market cap. ~AU$100 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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Exclusivity

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Scalable, economical GMP process for purifying exosomes

Tropism-conferring approach for engineering exosome surface proteins

Activity enhancing method for delivering RNA by exosomes

100% Exopharm

100% Exopharm

100% Exopharm

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

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. 10

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. 11

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. 12

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. 13

LOAD Creates High Copy-number EVs

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siRNA

EV-producing cells

siRNA loaded EV

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Analysis by Bioanalyzer qRT-PCR
0.010
Buffer control siRNA control siRNA loaded
0.008
0.006
0.004
0.002
0.000
Buffer control SNAIL siRNA
Depending on the conditions, siRNA copies per EV typically are between 500 – 1000
loading siRNA (in ng)
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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

LOAD Enhances Cargo Effect

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mCherry protein expression in cells treated with EVs containing mCherry RNA …

RNA Status 2021 Plans siRNA Sars-COV2 siRNA (~20 bases) mCherry (~700 bases) CFTR-GFP Currently in progress (~6.5k bases) …

Standard LOAD enabled mCherry RNA mCherry RNA

© 2021 Exopharm Ltd. 16

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. 17

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