evox therapeutics

Evox Therapeutics Solebury Trout Fall Private Company Showcase

15 October 2020

Evox Therapeutics – Corporate Presentation. All Rights Reserved.

• Nano-sized vesicles that are secreted by cells,

and are found in all biological fluids

• The natural way that cells safely and efficiently

deliver proteins and nucleic acids to other cells

• Exosomes have the potential to revolutionise

drug development and result in transformative

new medicines

• Evox is engineering exosomes to deliver drugs

to areas that are currently inaccessible

• Evox’s exosome therapeutics are non-

immunogenic and can be manufactured at

scale using well characterized human allogenic

cell lines

2

A disruptive approachExosomes as a new therapeutic modality

1. Multivesicular bodies bud inward to form small vesicles containing protein and RNA cargo

2. These vesicles are released by cells as exosomes, the body’s natural delivery system

3. Upon reaching their target, exosomes efficiently deliver their cargo inside the target cells

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2

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Evox Therapeutics – Corporate Presentation. All Rights Reserved.3

Our journey – supported by leading investors and partnersEvox Therapeutics

$13m Series A

April 2016

$46m Series B

Sept 2018Multi-target rare disease collaboration

$44m near-term / $882m total deal

March 2020

Clinical stage proprietary

rare disease pipeline

(2022-2023)

Evox founded

April 2016

Multi-target RNAi/ASO collaboration

$30m upfront / $1200m total deal

June 2020

Grant of broad exosome

patents on RNA drugs

and on tissue targeting

August 2019

Evox - 100 employees

2020


Executing on a pipeline-driven platform strategyOur strategy

• Proprietary pipeline focused on rare diseases with a clear causality that allows us to

advance into the clinic with an option to self-commercialise

• REPLACE (current): rapid acting protein replacement therapies delivering to tissues

that are otherwise inaccessible with current approaches

• CORRECT (near-term): deliver payloads with the ability to have both sustained

effect and allow intermittant re-dosing

Pipeline

assets

Technology

platform

• Proprietary DeliverEXTM exosome engineering platform covering a diverse range of

drug cargos

• Advanced manufacturing capabilities for a diverse range of drug cargos

• Dominant IP estate with full freedom to operate

Strategic partnerships: for large indications or to access disease or drug expertise


Non-immunogenic & titratable

hepatocyte delivery

• Fast-acting biologics

• Cytoplasmic expression

• Monogenic liver disease focus

Delivering long-lasting payloads

with intermittent dosing

• Long-lasting nucleic acid drugs

• Widespread biodistribution

• Overcoming cell tropism

Leveraging exosomes for competitive advantage

5

Advance our REPLACE and CORRECT pipeline and continue to build platform value

Current

REPLACE pipeline

Near-term

CORRECT pipeline

Targeted exosome delivery of

different payloads

• Small RNA and mRNA drugs

• Deliver to CNS & other tissues

• Collaborations with pharma

DeliverEXTM opportunities


• Fast-acting delivery of biologics to hepatocytes

• Deliver cytosolic proteins (expansion possible into trans-membrane proteins)

• Leverage the exosome’s efficient hepatocyte delivery and ability to re-dose

• Difficult or impossible to treat with enzyme replacement or AAV-based gene therapies

• Leverage immunosilent nature of exosomes to avoid loss of efficacy due to innate and

acquired immunogenicity inherent in other approaches

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Evox’s USPsREPLACE pipeline


Partnered

programs

Internal

programs

Discovery Preclinical IND Enabling Clinical

RNAi/ASO

5 undisclosed targets

EVX-102: Argininosuccinic aciduria

Protein exosomes

EVX-103: Citrullinemia Type 1

Protein exosomes

Undisclosed

Protein / mRNA

Rare

Meta

bolic

Ure

a C

ycle

Dis

ord

ers

Rare

dis

eases

EVX-101: Niemann-Pick disease type C

Protein exosomes

Neuro

logic

al

RNAi: RNA interference; ASO: anti-sense oligonucleotide

PKU

Protein / other modalities

Pipeline opportunities

Protein / mRNA exo.Oth

er

Internal programs in the orphan space and extensive options for partnered programsEvox pipeline overview

CTA 2022

CTA 2022

CTA 2023


Production of engineered exosome therapeuticsRobust and scalable process using human allogeneic cell sources

2 different exosome drug loading strategiesEndogenous: 1-step genetic engineering of exosome-producing cells

Exogenous: 1-step loading of exosomes with existing drugs

Engineering and producing exosomes to contain drugsDifferent strategies to load various types of drugs combined with scalable production

Adapted from Wiklander et al.

(2019) Science Transl. Med.

Proteins

Antibodies

Small molecules

RNAi & anti-sense

mRNA

AAV

Exogenous

loading

Endogenous loading


Proprietary in-house exosome production

• Identification and optimisation of an exosome-producing cell is

key to therapeutic development

• Evox has developed state of the art analytical tools to

characterise exosomes

• Evox has conducted a large screen and identified multiple

different platform producer cell lines

• Evox advancing a GMP-ready scalable immunosilent

exosome-producing cell

• Evox also generating other GMP exosome-producing cell lines

Leading the field in exosome analytics and process development

Exosome screening

Exosome proteomics Single exosome analysis

Surface phenotyping


Important attributes

Exosomes as therapeutics

Adapted from Heusermann et al., (2016) J. Cell Biol. 213:173-184

• Purified exosomes are well tolerated in

humans, even upon repeat administration

• Blood transfusions contain large amounts

of exosomes and are performed routinely

• Variety of payloads are continuously and

safely delivered safely via exosomes

without immune recognition

• Evox’s engineered exosomes have shown

no toxicity in pre-clinical species including

non-human primates

Exosome uptake into cells is distinct

from lipid nanoparticles

Exosomes Lipid nanoparticles


• Niemann-Pick Disease Type C: rare lysosomal

storage disorder affecting 1 in 120,000 people

• Loss of function mutations in the NPC1 lysosomal trans-

membrane transporter protein

• Accumulation of cholesterol and glycolipids inside patient

cells

• Progressive neurological disease responsible for

disability and premature death

• Toxic build up inside cells seen in multiple organs, most

notably CNS, liver, and spleen

• Limited treatment options available

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First-in-class therapy for Niemann-Pick Type CEVX-101: Exosome-mediated NPC1 replacement program

EVX-101: Exosome containing the membrane transporter NPC1, which is defective in Niemann-Pick disease type C

13 T

M d

om

ain

s

Crystal structure

of human NPC1

Cryo-EM of EVX-101

* Based on analysis completed for Evox by LEK Consultants (Sept 2018)


Comparison of native and NPC1-engineered exosomesEVX-101: Phenotypic correction in patient-derived cells

Untreated EVX-101 Unloaded exosomes

Intracellular free cholesterol content as judged by filipin staining at 72 hrs following no treatment

(untreated) or treatment with native unloaded exosomes or NPC1 exosomes (EVX-101)


• ASA is a rare autosomal recessive life-threatening urea cycle

disorder caused by a deficiency in the ASL enzyme

• ASL enzyme deficiency results in elevated levels of ammonia in the blood and

a defective nitric oxide pathway

• Long-term complications include liver dysfunction and neurocognitive deficits

• No curative approved therapy

• Despite standard of care (dietary measures, ammonia scavengers) patients

often have significant morbidity and many do not survive into adulthood

• Straightforward clinical readouts exist

• A variety of well-established clinical and biomarker readouts exist

• Potential 2022 CTA candidate

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First-in-class therapy for argininosuccinic aciduria (ASA)EVX-102: Exosome-mediated urea cycle replacement program

EVX-102: Exosome containing the human ASL enzyme, which is defective in argininosuccinic aciduria

Cryo-EM of EVX-102


EVX-102: in vivo reduction in multiple biomarkers

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ASL-hypomorphic mice systemically treated with ASL exosomes

• Single treatment with ASL exosomes leads to

rapid reduction of disease biomarkers in mice

• Reduction in clinically important plasma

ammonia and argininosuccinic acid levels

WT EXO EXO-hASL

0

20

40

60

80

100

Co

nc

en

tra

tio

n (

µm

ol/

L)

Plasma ammonia levels

**

ns

WT EXO EXO-hASL

0

400

800

1200

Co

nc

en

tra

tio

n (

µm

ol/

L)

Plasma Argininosuccinic Acid

***

ns

Unloaded exosome ASL exosomeWT mice

ASL-deficient mice

Unloaded exosome ASL exosomeWT mice

ASL-deficient mice

ASL enzyme

Upstream

Biomarkers


Other Evox internal programs

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• Citrullinemia type I (ASS Deficiency)

• Urea cycle disorder with similar incidence/severity as ASA

• Main target cell is the hepatocyte and defective ASS enzyme is directly upstream of ASL enzyme

• Evox is pursuing a protein replacement strategy similar to ASA

• Phenylketonuria (PKU)

• Inborn error of metabolism liver disorder with high incidence of 1:12,000

• Defect in PAH enzyme results in an inability of hepatocytes to breakdown phenylalanine which then accumulates

in blood tissue and affects organs such as the brain leading to neurocognitive defects

• Dietary regimen has poor adherence and enzyme substitution therapy drug has high rate of anaphylactic

reactions, limiting its use

• Pursuing both a protein replacement strategy as well as undisclosed approaches using long-acting payloads


• Design of new exosome drugs is modular

• From ideation to having an exosome-based

drug prototype ready for in vivo testing in as

little as 2-3 months

• Exosome-based drugs can possibly go

from project initiation to CTA/IND in 18-24

months

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Rapid development of new exosome drugs from inception to CTA/IND in 18-24 monthsExosome therapeutics: a modular platform


Potential for improved uptake, sustained retention, and long-lasting effect using exosomes CORRECT pipeline

Rapid and sustained CNS uptake after intrathecal delivery of

non-targeted exosomes in non-human primate• Rapid and sustained brain uptake of labeled

exosomes after direct CNS injection in

non-human primates

• Rodent studies confirm improved distribution

and efficacy of direct exosome-mediated CNS

delivery

• Direct exosome delivery to the CNS and other tissues represents another area for pipeline

growth

• Exosomes may enable increased uptake, broader distribution and longer drug retention to result in long-

lasting effect

• Potential to deliver not only biologics but also long-lasting nucleic acid drug cargos

Intr

ath

eca

l (I

T)


Advancing the platform to create new therapeuticsDeliverEXTM platform

• World-leading exosome engineering to load

drugs and targeting ligands into/onto

exosomes

• In vivo tissue targeting of exosomes

• Wide variety of therapeutic payloads

including nucleic acid-based drugs

Exosome engineering to load drugs and target tissues

Proteins

Antibodies

Small molecules

RNAi & anti-sense

mRNA

AAV

Exogenous

loading

Endogenous loading


Potential to open nucleic acid therapeutics to currently inaccessible tissues Exosome delivery of nucleic acids

Evox exogenous small RNA loading

Evox endogenous mRNA loading

• Delivery of siRNA, mRNA, and gene editing

therapeutics limited to a few cell types/tissues

• Exosomes can effectively deliver nucleic acids

to non-hepatic cell types in vivo

• Targeted delivery to CNS, muscle, and tumours reported

• Evox is using exosomes to fully exploit siRNA,

mRNA, and gene editing-based therapeutics

• Targeted delivery of different cargos to various tissues

• Evox and are developing a mRNA exosome

therapeutic for the treatment of a rare disease

• Evox and are working on RNAi/ASO exosome

therapeutics for the treatment of 5 neurological diseases


Dominant patent portfolio with breadth and depth Evox’s unrivalled IP position

Foundational IP estate broadly covering all major technology areas

Full freedom to operate

~200 worldwide patent assets covering all aspects of exosome therapeutics

>10 granted patents

PROTEIN THERAPEUTICS

Surface receptors, proteins and

antibodies. Intracellular delivery of

proteins and Abs

RNA DELIVERY

Delivery of synthetic RNA

therapeutics. mRNA loading and

delivery technology

EXOSOME TARGETING

Unique tissue targeting strategies.

Cell source profiling and exosome

fingerprinting

CMC & PURIFICATION

Downstream purification

technology. Exosome analytics

and quality control


Uniquely placed to deliver on the potential of exosome therapeuticsLeadership team

Tony de Fougerolles

Chief Executive Officer

2017

• 20+ years R&D

experience developing

platform technologies &

translating assets into

clinical settings and

approved drugs

• Instrumental in

developing 3 new multi-

billion dollar drug

platforms (RNAi, mRNA,

single domain Ab)

• Former CSO at Ablynx

and Moderna

• Executive management

positions at Alnylam and

Tolerx

• PhD in Immunology from

Harvard University

Per Lundin

Chief Operating Officer

2016

• Co-founder of Evox

• 10+ years experience

founding, leading and

advising biotech

companies

• European Patent

Attorney

• Previously heading up

European business

development for

Thomson Reuters IP &

Science

• Founder & CEO of

IsletOne Therapeutics

• PhD from the Karolinska

Institute

• MBA from Stockholm

University

Bo Kara

VP Process Development

2018

• 30+ years experience

developing scalable

manufacturing &

analytics for biologicals

products

• Deep knowledge of

technical, regulatory and

commercial aspects of

drug development

• Former Head of Process

Development – Cell &

Gene Therapy at GSK

• Head of R&D at Fujifilm,

leadership roles at AZ

within manufacturing

and CMC

Simon Dew

VP Business Development

2019

• 20+ years experience in

pharmaceutical

Business Development,

Product Portfolio

Strategy and operational

experience in

international markets

• Previously VP Corporate

Strategy at Gyroscope

Therapeutics and

leadership roles at

Astellas

• Board advisor to

Sunstone Capital

Kerry Jaycock

Head of Human Resources

2019

• 15 year experience

across a variety of

industry sectors

• Expertise in

organisational change

and employee

engagement with a

focus on culture

• Extensive biotech

experience and

previously head of HR at

Immunocore, a leading

TCR company

Sonya Montgomery

Chief Medical Officer

2020

• A physician with 20

years clinical

development experience

• Expertise in early

development including

translational medicine in

gene therapy, small

molecules and biologics.

• Former head of Clinical

development at

Gyroscope Therapeutics

• Extensive biotech and

Pharma development

experience in roles at

ProQR and Pfizer

David Lowe

VP Research

2020

• 20+ years biotech and

large pharma R&D

experience in advancing

protein and Ab-based

drugs and exploring new

biologics platforms

• Former Sr, Director at

Astra Zeneca in charge

of Biologics Engineering

• Former global head at

AZ of In vivo Expressed

Biologics focused on

AAV, DNA, mRNA and

exosomes

• Led antibody teams and

projects at CAT

• PhD in from the

University of Cambridge


Clinical development for internal pipeline and collaborating with partners in strategic areasAdvancing exosome therapeutics

Pipeline progression

• Expected 2022 CTA for ASA

• Several other possible 2022-2023 CTA or IND candidates

• Several Takeda-partnered programs advance including NPC

• Up to 5 Lilly-partnered neurology RNAi/ASO programs

• Growth of pipeline to include a half-dozen other related rare disease indications

Platform development

• In vivo tissue-targeting to CNS and other organs

• In vivo mRNA delivery

• Exosome delivery of other drug cargos

• Expansion of in-house manufacturing

• Leverage platform through select partnerships

Evox Therapeutics Solebury Trout Fall Private Company Showcase

15 October 2020

evox therapeutics

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