ENTROPY NEURODYNAMICS LIMITED — Investor Presentation 2021

Nov 15, 2021

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ASX ANNOUNCEMENT

Exopharm to Present at Key Exosome Industry Event

16 November 2021, Melbourne, Australia :

Exopharm Limited (ASX:EX1), a clinical-stage, global leader in exosome medicines, announces that Chief Commercial Officer and Deputy CEO, Dr Chris Baldwin, will present at the 3[rd] Exosome Based Therapeutic Development Digital Summit on 16 November (2:00PM US Eastern Time, 6:00AM AEDT).

The presentation entitled “Recent Advances in Cation Exchange Purification of Exosomes” will highlight recent developments that Exopharm has made with its LEAP technology for the purification of exosomes.

The Summit, subtitled “ Successfully Source, Characterize & Load Clinically Relevant Exosome Therapeutics for Accelerated Development & Commercialization ”, is the key international industry-dedicated exosome meeting.

A copy of Dr Baldwin’s presentation slides is attached.

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

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: Suite 201, 697 Burke Road Camberwell 3124 Email: info@exopharm.com Web: www.exopharm.com

ABOUT EXOPHARM

Exopharm Limited (ASX:EX1) is a clinical-stage biopharmaceutical company at the forefront of transformative medicines using exosomes, or extracellular vesicles (EVs), and is pursuing a pipeline-driven platform strategy.

Exosomes can be loaded with a variety of active pharmaceutical ingredients (APIs) and can be targeted to selected cell and tissue types (tropism) – improving the safety -profile of the APIs and providing better treatments.

Exosome delivery of DNA and other gene therapies into the nucleus of the patient’s cells can improve treatment of inherited medical conditions.

Exosomes are an alternative means of drug delivery inside the body, alongside technologies such as lipid nanoparticles (LNP), cell-penetrating peptides, viral vectors and liposomes. The drug delivery industry is growing at a compound annual growth rate (CAGR) of 5% and is currently valued at about US$175 billion ($233 billion).

Exopharm’s exosome technologies meet important needs for the success of exosome medicines – LEAP manufacturing technology, LOAD API loading and EVPS tropism.

Exopharm’s suite of exosome technologies enables its own pipeline of exosome medicines – each aimed at delivering a transformative medicine for an unmet medical need.

Exopharm’s intellectual property is also available under licences or partnerships to empower others to build their pipelines around the benefits of exosome medicines.

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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Recent Advances in Cation Exchange Purification of Exosomes

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November 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

Agenda

1. Introduction to Exopharm and LEAP

2. Recent Developments

3. Summary

© 2021 Exopharm Ltd. 3

Exopharm

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• Australian development-stage biotechnology company dedicated to bringing exosome medicines to patients

• 50 staff based in Melbourne

Commercial-scale exosome purification capabilities

Engineered exosomes for selective tissue targeting ( tissue tropism )

API cargo loading for exodrug delivery

Modular Platforms Enabling Exo-Medicines Across Broad Disease Categories [*]

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Engineered Exosomes

Exo-Tropism – targeted delivery

• Externally presented targeting molecules

• Can be selected for selected cell / tissue

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type

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Exo-Medicines

• Can aid crossing the blood-brain barrier

• Non-viral, human molecules

Exosome purification technology

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Precision-engineered medicines for select tissue targeting and optimized cargo delivery

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Exo-Cargo Loading

Proprietary technology to purify exosomes in largescale and as clinicalgrade product

▪ AAV

• DNA

• CRISPR

• Small molecules

• Nucleases

• RNA

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Rare Diseases
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Cancers
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Viruses
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Neurological
Diseases
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Ocular
Disorders
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Naïve Exosomes

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Commercial-scale

naïve exosome purification from adult stem cells, blood

products etc

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• Harness the regenerative power of adult stem cells or donor blood material

• Cell-free product

• Improved logistics and supply-chain compatibility

• Proven safety

• Low immunogenicity

• Cross tissue barriers (e.g. blood‐brain barrier)

• High biocompatibility

• Illustrative

© 2021 Exopharm Ltd.

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Starting with the End in Mind
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Same Objective:

Different Approaches

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Exosome medicines will be
a major modality for
delivering precision
medicines
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• Identify the indication

• • Demonstrate efficacy

• • Solve scalability later

• • Invent manufacturing process that is: • General

• • Scalable

• • Economical

Product First • Demonstrate efficacy Approach • Solve scalability later (others) • Invent manufacturing process that is: • General Process First • Scalable Approach • Economical (Exopharm) • Solve scalability upfront • ™ LEAP

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LEAP Chromatography
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1. Biofluid is loaded onto LEAP chromatography column

2. Exosomes bind to the LEAP matrix

3. Impurities stay in the flow through

4. Residual impurities washed out

5. Exosomes retained

6. Exosomes recovered with elution buffer

7. Column cleaned & regenerated

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Exosomes
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exosomes
Exosomes
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© 2021 Exopharm Ltd. 7

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LEAP Process (Platelet-Exosomes) Example
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Load Wash Elute
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• LEAP columns can be sanitized and reused

• Concentration factor ~ 70x

LEAP generates distinct elution peaks

© 2021 Exopharm Ltd.

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Purity Analysis via AF4-MALS:
Ultracentrifugation (UC) and LEAP
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Light scattering Radius of exosomes
Impurities
Light scattering Radius of exosomes
Impurities observed from UC
separations are absent with LEAP
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Ultracentrifugation
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LEAP Purfies Biologically Active Particles
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Human Dermal Fibroblast Proliferation Assay
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1.6
1.5
1.4
1.3
1.2
1.1
1.0
0.9
Negative Raw Media Unretained LEAP Positive
Control Particles Captured Control
Exosomes
Cell Index (normalized)
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Unretained particles activity indistinguishable from negative control LEAP captured exosomes demonstrate higher activity than raw media

LEAP is purifying active particles away from inactive ones

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Exopharm Invented Commercial-scale
Exosome Purification Technology
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State of the Art, Exosome Purification as of June 2020*

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AF4
Research Scale
Nano-FCM
UC
Immunoaffinity
Diagnostic Scale
Commercial reagents
Microfluidics Phase I Scale
Density gradient
Phase II/III Scale
SEC
Commercial
Filtration
Manufacturing
Scale
Low
SCALABILITY High
High
COST
Low
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LEAP Technology:

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1. A recognised game-
changer in exosome
manufacture
2. Industry-standard
equipment / processes
3. Low-cost
consumables
4. Modular system
scalable to meet
global commercial
supply
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** LEAP assessment from Exopharm, based on industrial use to date; LEAP Patents granted in two countries and progressing through National phases at present

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

© 2021 Exopharm Ltd.

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LEAP is Fully Scalable and cGMP Ready
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Commercial Manufacture Scale-up, Clinical Trials AKTA process™ AKTA pure 25 Proof-ofConcept Scale AKTA ready™

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LEAP into Today
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Public Listing

First LEAP patent granted

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Second LEAP agreement for regenerative medicine products

Ready to Go Commercial

Dec 2018

Apr 2021

Sep 2021

• Tech transfer

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Jun 2021 First commercial collaboration for platelet exosomes

Sep 2021

Oct 2020

US patent approved to issue

PLEXOVAL II Clinical trial

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• Exploration tools for small-scale evaluations

• Custom LEAP for specific applications

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Scalable, economical GMP process for purifying Exosomes

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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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• Initially developed in 2016

• Cation exchange process

• Exosomes have a net negative surface charge, but local positive surface charges allow for Exosomes to be reversibly bound using cation exchangers with unique ligand geometries

• This discovery applies to an entire class of ion exchangers , including commercially available resins from leading manufactures

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Exosome medicine companies and researchers

• Start small scale

• Expand formats, scales

• High yield industrial process

Companies with cation exchange products covered by LEAP IP

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1. Recent Developments • Tech transfer • Selection tools • Source-specific solutions

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• Standardized documentation, process videos

• Supported by separate customer service group

• Technical team currently expanding considerably

• Exploring strategic R&D and commercial partnership

• International

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Scaling Down to Scale Up
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1×10 [11]
5mL Load
8×10 [10] 1mL Load
6×10 [10]
4×10 [10]
2×10 [10]
0
Elution volume (mL)
0.10.20.30.40.50.60.70.80.9 11.11.21.4
particle conc (p/mL)
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Flexible evaluation tools

• Any size columns (200 µL – 50 mL +)

• • Gravity or pressure driven

• Particle capture profiles align closely with across various sized columns

• Benefits of small scale

• Ability to quickly screen multiple resins against a specific feedstock

• Quickly test multiple parameters via design of experiment (DOE) principles

• Better suited for cell line development

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Various Exosome Sources Bring Unique
Purification Challenges
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LEAP purification runs by exosome source

Suspended cells

• Stronger binding

• • More initial Donor sourced •

• protein Albumin

• Lipoprotein

Adherant cells

• Lower initial exosome concentrations

• Extracellular matrix proteins

© 2021 Exopharm Ltd.

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Optimized LEAP Handles Them All
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LEAP process, donor platelets

LEAP process, adherent cells

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Starting media has different

• Initial concentration of exosomes

• Non-exosome particles (cellular debris)

• Overall protein quantities and sizes (e.g. lipoproteins)

• Output is comparable

LEAP captures exosomes regardless of source

© 2021 Exopharm Ltd.

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LEAP is Highly Tuneable to Meet Specific Exosome
Product and Process Requirements
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100%
Customized
50%
More yield,
Greater purity greater purity
0%
Standard
-50%
More yield
-100%
-100% -50% 0% 50% 100%
Removal
Relative Protein
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Full Exploration of Numerous Resin Options

• Explore range of commercially available resins

• Design experiments to cover loading, wash, and elution variables

• Determine specific resins and experimental conditions for specific source materials and output requirements

Design of Future Cation Exchange Media

• Identify novel ligands for exosome specificity

• Leverage variety of substrate types (gels and structured)

Relative Yield

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1. Summary

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Key Takeaways

LEAP patents cover commercial and novel chromatography products that purify exosomes

Exopharm has optimized and transferred the LEAP technology to multiple collaborators, each with distinct source materials

LEAP has the characteristics necessary to become the STANDARD purification process for exosome medicines

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© 2021 Exopharm Ltd. 23
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Going Big, Together

Exopharm works with strategic partners to bring exosome medicines to reality

Exopharm is open to partnerships:

• Technology transfer and non-exclusive out-licensing of existing IP

• Collaborative extension of IP to new uses, efficiency improvements, adjacent processing techniques, etc

© 2021 Exopharm Ltd.

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Thank you

Exopharm Ltd (ASX:EX1)

Dr Chris Baldwin Deputy CEO & Chief Commercial Officer chris.baldwin@exopharm.com www.exopharm.com