ENTROPY NEURODYNAMICS LIMITED — Investor Presentation 2021

Feb 15, 2021

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ASX ANNOUNCEMENT

Exopharm presents at Bio CEO & Investor Digital Conference

16 February 2021, Melbourne, Australia : Exopharm Limited (ASX:EX1) announces that the Chief Commercial Officer, Dr Chris Baldwin, will present to the Bio CEO & Investor Digital Conference on 16 - 18 February 2021.

Dr Baldwin’s presentation entitled “The Global Growth of EV Medicines and the Year We LEAP” is attached.

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

Company and Media Enquiries:

Dr Ian Dixon, MBA Founder and Managing Director P: +61 (0)3 9111 0026 ian.dixon@exopharm.com

Rudi Michelson Monsoon Communications Tel: +61 (0)411 402 737 rudim@monsoon.com.au

Join our mailing list to receive updates:

http://exo.ph/ExoMails www.exopharm.com P: +61 (0)3 9111 0026

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 transformative 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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The Global Growth of EV Medicines and the Year We LEAP

Investor Presentation

16 February 2021

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.

© 2021 Exopharm Ltd. 2

Exopharm Ltd

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Overview

• Exopharm is a clinical stage company at the forefront of developing transformative medicines based upon exosomes (EVs)

• 40 staff based in Melbourne, Australia; 2 staff based in Europe

• Publicly-traded on the ASX (ASX:EX1) (listed Dec 2018) Current market cap: AU$ ~100 million, 139 million shares on issue

Priorities

• Empower exosome medicine discovery globally

• • Build general EV engineering, manufacturing and characterization platform

• Establish regulatory pathways for EV products through early phase clinical development

• Partner with established biopharmaceutical companies to ensure the broadest application of the technology possible

• Generating revenue

© 2021 Exopharm Ltd. 3

EVs: Nature’s Solution to Cellular Coordination

Extracellular Vesicles (or EVs, also referred to as exosomes) are natural nanoparticles that transfer cargo between cells

EVs consist of three parts:

1. Package : Outer membrane that forms the EV

1. LIPID BILAYER (packaging)

3. RNA, PROTEINS, LIPIDS (cargo)

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2. Address : External proteins that determine which cells receive an EV

3. Cargo : Instructions (RNA) and building materials (proteins)

2. PROTEINS (addressing)

• © Exopharm Ltd. 4

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© 2021 Exopharm Ltd. 5

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Pfizer and Moderna vaccines deliver RNA to cells using artificial nanoparticles (LNPs)

However, LNPs have major limitations for drug delivery:

• Anti-LNP immune response

• Lack of specific address

• Inefficient cellular uptake

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EVs overcome all biological
limitations of LNPs
But without economical
purification, EVs have not been
a legitimate option
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© 2021 Exopharm Ltd. 6

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Promising global results

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But without LEAP*:

Scaling up to Phase II trials will be very expensive

Scaling to Phase III or commercial will be near impossible

• or some new discovery

Every new result increases the potential value of LEAP

Every new result de-risks Exopharm’s EV programs

© 2021 Exopharm Ltd. 7

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Scalable, economical GMP process for purifying EVs

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Charged ‘R’ groups
spaced along
backbone at distance
of around 5Å
5 Å
Carrier can be resin
or membrane
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© 2021 Exopharm Ltd. 8

LEAP is the Only Known Technology for Commercial-scale EV Purification

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

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AF4
Research Scale
Nano-FCM
UC
Immunoaffinity
Commercial reagents Diagnostic Scale
Microfluidics
Phase I Scale
Density gradient
Phase II/III Scale
SEC
Filtration
Commercial
Manufacturing
Scale
Low Scalability High
High
Cost
Low
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Unlike all alternatives,
LEAP technology:
1. uses industry-standard
equipment/processes
2. uses low-cost, reusable
consumables
3. scales economically
beyond thousands
of doses
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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

© 2021 Exopharm Ltd. 9

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Companies with assets covered by LEAP IP

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Companies developing EV medicine pipeline

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© 2021 Exopharm Ltd. 10

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. 11

Today, LEAP Presents Four Distinct Paths to Revenue (“LEAP Inside”)

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1. Internal Program Enablement

2. All Naïve and Engineered EV Products

3. Very large upside, slower to monetise (> 3 yrs)

4. Branded LEAP Columns Sold to Academic Researchers • Small, quick potential (< 1 yr)

5. Exploring OEM partners

6. Know-how/Tech Transfer to Biotechs seeking to scale

7. Potential collaboration agreements with peer EV companies and pharma companies building internal EV expertise

8. Considerable medium term revenue (1 – 3 yrs)

9. Licenses for Commercial Use

10. Multiple alternatives leading to LEAP enabling entire EV medicine field

11. • Major long-term revenue stream (>4 yrs); exploring revenue partner

© 2021 Exopharm Ltd. 12

Naïve Program Advances Regulatory Progress Across All EV Products

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Step-wise progression to regulatory acceptance of EV medicines possible due to consistent process Regulatory Perspective on EV Sources iPSC EVs Primary MSC EVs PLT EVs Allogeneic Platelet EVs Autologous

© 2021 Exopharm Ltd. 13

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“A prospective, randomised, double blind, placebo controlled , single dose, single site phase I study to assess the safety and biological activity of a Human nonautologous platelet derived extracellular vesicle therapy vs placebo on wound healing rate following skin punch biopsy in healthy volunteer adults” (Trial registration number CT-2020-CTN-01678-1) Final dosing: Dec 2020 Final follow-up: Jan 2021 Final report: around Mar 2021

© 2021 Exopharm Ltd. 14

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© 2021 Exopharm Ltd. 15

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Strategy

• Use Naïve EV programs to build manufacturing and regulatory expertise across both Naïve and Engineered EVs

• Leverage lower COGs and demonstrated safety profile as a "fast follower" to cell based regenerative medicines

Clinical Milestones

Platelet EVs

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Autologous Phase I (2020) Allogeneic Phase I (2021)

MSC EVs Allogeneic Phase I (2022)

© 2021 Exopharm Ltd. 16

Unique, Powerful Technology Underpins Engineered EV Programs

Exclusivity Applicability

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• Natural EVs (e.g. blood, 100%

• plant, bacterial)

• • Exopharm Engineered EVs

• • Natural EVs 100%

• • Engineered EVs Exopharm

Scalable, economical GMP process for purifying EVs

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Activity enhancing method for delivering RNA by EV

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• Engineered EVs only

• • Can also be used for 100% tracing and protein Exopharm cargo

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Tropism-conferring* approach for engineering EV surface proteins

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• Tropism is the preference for an EV to enter a specific cell-type

© 2021 Exopharm Ltd. 17

LOAD: More RNA Cargo, More Effect

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Activity enhancing method for delivering RNA by EV

• Cells have sorting machinery that can transfer specific RNA sequences into EVs

• LOAD attached to an RNA cargo directs the sorting machinery to preferentially pack RNA cargo into EVs

• LOAD increases the efficiency of RNA cargo loading by 10 – 100-fold

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Standard approach
RNAi
EV with low copy
No preferential
count of target RNA
loading
LOAD+RNAi 10-100x increase in
LOAD engages cellular
RNA copy count
sorting machinery
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© 2021 Exopharm Ltd. 18

EVPS: Construct Approach

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Tropism-conferring approach for engineering EV surface proteins

1. Design construct based on VSVg viral coat protein:

Cargo: Cytoplasmic domain for proteins carried as cargo

VSVg: Transmembrane domain passes through cell and EV bilipid layers CTD: Cell-targeting domain for externally facing proteins

CTD Cell-targeting domain Cytoplasmic domain

1. Engineer into producer cell line using plasmid vector

EVPS EV from engineered producer cell

Note: VSVg = vesicular stomatitis virus glycoprotein

© 2021 Exopharm Ltd. 19

Fortrexo CoV: Target anti-CoV siRNA to ACE2+ Cells

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Engineered
Cells
CoV Spike on EV
GFP/RFP COV2 S-protein
Surface targets ACE2+
cells
Reporter
cargo ACE2
tropism
RNAi designed to
stop CoV replication An alternative answer to vaccines
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© 2021 Exopharm Ltd. 20

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Custom addressing - targeting EEVs to selected cell types

Custom medicines ‘Drug’ + cargoes e.g. small = molecules, RNAi, siRNA, mRNA

Viruses

Cancers

Neurological Rare diseases diseases

Partnering Capabilities

• Protein and nucleic acid additions to EVs

• Fully-scalable proprietary purification technology

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Cognevo: EVs Enter Brain Cells

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EVPS to enhance BBB penetration

LEAP-purified MSC-EVs are taken up by human neuronal-like and glial-like cell types in vitro

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Blue - glial cells (LN18), Green - EVs 10-15% uptake

Blue - neuronal cells (SH-SY5Y), Green - EVs 40% uptake

• Developing constructs to confer neurotropism through surface protein expression

• Collaborations with academic KOLs to identify and test peptide, scFv and other constructs

Advanced cargo options

• Delivering gene therapy alternatives (such as RNA or protein) through BBB

• Multiple academic collaborations in place

© 2021 Exopharm Ltd. 22

Engineered EV Deals

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EV Company IP Status Pharma Partner Date Area Upfront Milestones
Jun
CNS > $50 mln $1.7 billion
2020
Mar Rare
$63 mln $1.3 billion
2020 diseases
Jan
Cancer $77 mln $1.8 billion
2019
Jun
CNS > $100 mln Not disclosed
2020
Target: 2021
As of Jun 2020
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© 2021 Exopharm Ltd. 23

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Exo harm has a Direct Path to Revenue p

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Jan – Jun 2020 Jul – Dec 2020 Jan – Jun 2021 Jul – Dec 2021
EEV IP Added Additional IP Additional IP
Economic results Bioprocessing Licensing Revenue
PLEXOVAL I PLEXOVAL II Partnering Plan Tech Transfer
Non-clinical results Dose and Formulation
Mfg. facility
Anti-CoV patent lodged POC results SARS-COV2 in vitro
CNS design Acad. Partnership
EEV Partnership
Naïve EVs
EVs
Engineered
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= Key Value Driver

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Transformative Medicine

© 2021 Exopharm Ltd. 25