Stoke Therapeutics : Corporate Presentation - May 2024

Stoke Therapeutics

NASDAQ: STOK

May 2024

© Copyright 2024 Stoke Therapeutics

Disclaimer

This presentation has been prepared by Stoke Therapeutics, Inc. ("Stoke" or "us") for informational purposes only and not for any other purpose. Nothing contained in this presentation is, or should be construed as, a recommendation, promise or representation by the presenter or Stoke or any officer, director, employee, agent or advisor of Stoke. This presentation does not purport to be all-inclusive or to contain all of the information you may desire. Information provided in this presentation speaks only as of the date hereof. Stoke assumes no obligation to publicly update any information or forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments, subsequent events, or circumstances after the date hereof, or to reflect the occurrence of unanticipated events.

This presentation contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, the ability of STK-001 to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior or cognition at the indicated dosing levels or at all; the timing and expected progress of clinical trials, data readouts, regulatory decisions and other presentations for STK-001 and STK-002; the timing of regulatory interactions or the outcomes thereof; our future operating results, financial position and cash runway; and our expectations, plans, aspirations and goals, including those related to the goals of our collaboration with Acadia. Statements including words such as "anticipate," "plan," "will," "continue," "expect," "ongoing," or "potential" and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause our results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: our ability to advance, obtain regulatory approval of, and ultimately commercialize our produce candidates; the timing of data readouts and interim and final results of preclinical and clinical trials; positive results in a clinical trial may not be replicated in subsequent trials or successes in early stage clinical trials may not be predictive of results in later stage trials; our ability to fund development activities and achieve development goals; our ability to protect our intellectual property; global business, political and macroeconomic conditions, including inflation, interest rate volatility, cybersecurity events, uncertainty with respect to the federal budget, instability in the global banking system and volatile market conditions, and global events, including public health crises, and ongoing geopolitical conflicts, such as the conflicts in Ukraine and the Middle East; and other risks and uncertainties described under the heading "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2023, our quarterly reports on Form 10-Q and the other documentation we file from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this presentation, and we undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

By attending or receiving this presentation you acknowledge that you are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made; you will be solely responsible for your own assessment of the market and our market position; and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of Stoke.

© Copyright 2024 Stoke Therapeutics	2

OUR GOAL:

Upregulate protein expression to treat

the underlying cause of severe genetic diseases

Stoke's pipeline offers potential first-in-class disease modifying new medicines

for diseases caused by protein insufficiency

STK-001 for	STK-002 for Autosomal	Rett syndrome,	And beyond…
Dravet syndrome	Dominant Optic Atrophy	SYNGAP1	~6,500 additional genes
	(ADOA)
A severe and progressive	Severe and rare genetic	with TANGO
genetic epilepsy	The most common inherited	neurodevelopmental diseases	target signatures
	optic nerve disorder

© Copyright 2024 Stoke Therapeutics

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Advantages of Stoke's Approach vs. Other Genetic Approaches

Selectively boosts expression	No observed unwanted	Utility across small and large
only in tissues where the	off-target genetic effects	gene targets and mutations
protein is normally expressed

Does not	Ability to control dose level	Simple and scalable
alter DNA	and duration	manufacturing

© Copyright 2024 Stoke Therapeutics

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Haploinsufficiency without TANGO-ASO

= 50% functional protein

TANGO: Targeted Augmentation of Nuclear Gene Output. NMD: nonsense-mediated decay

Haploinsufficiency with TANGO-ASO

Increased functional protein expression

Dravet Syndrome: A Severe, Progressive Genetic Epilepsy

85%

of cases caused by a

HAPLOINSUFFICIENCY

of the SCN1A gene

RESULTING in

50%

NaV1.1 protein

expression

1 out of 16,000

babies are born with Dravet syndrome

Up to	of children and adolescents with Dravet
20%	syndrome die before adulthood, due to
SUDEP1, prolonged seizures, seizure-
related accidents or infections

Seizures are not adequately controlled in

90% of people with Dravet syndrome

~35,000

people affected in the U.S., Canada, Japan, Germany, France and the UK

Dravet syndrome is not concentrated in a particular geographic area or ethnic group

1 Sudden Unexpected Death in Epilepsy

Sources: Symonds, J. et al., Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants. Brain, 2021.

2018 Health Advances Report; Djémié et al., Molecular Genetics & Genomic Medicine, 2016; Lagae et al., Developmental Medicine & Child Neurology, 2017; Wu, Y. et al., Incidence of Dravet Syndrome in a US Population. Pediatrics, 2015. Nabbout et al., Orphanet Journal of Rare Diseases, 2013

© Copyright 2024 Stoke Therapeutics

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The Effects of Dravet Go Beyond "Just Seizures"

Intellectual Disability

& Developmental Delays

"Over time, we have seen slow, steady

decline in all areas, from speech, to mobility,

endurance, loss of energy, tolerance for

stimulation, stamina, etc."

Language & Speech

Disturbances

"At age 19, [our son] stopped talking, seemingly losing his capacity for speech

overnight. Most days he is silent, and though he can understand simple conversation he is

largely unable to express himself."

Source: Voice of the Patient Report Published by the Dravet Syndrome Foundation, May 2022

Movement & Balance

"We're disappointed when [our son's] physical activity is limited and the short walk or visit that we plan with his grandmothers must now be changed to a longer wheelchair ride."

Sleep Abnormalities

"Every single night, he has seizures in his sleep.

In addition to all of the other comorbidities of DS, he's robbed of the basic human necessity of getting a good night's sleep. This impacts our entire family, as it is hard to function on

so little sleep day after day."

© Copyright 2024 Stoke Therapeutics	8

STK-001 is on Track to be the First Disease-Modifying Medicine to Treat the Underlying Cause of Dravet Syndrome

Multiple medicines available for	No medicines currently available for
Seizure management	Dravet syndrome
	management

Despite these treatments, seizures are not adequately controlled in 90% of patients with Dravet syndrome

Available medicines used to control seizures:

•	Acetazolamide	•	Felbamate	•	Rufinamide
•	Benzodiazepines	•	Fenfluramine	•	Stiripentol
•	Brivaracetam	•	Lamotrigine	•	Topiramate
•	Cannabidiol	•	Levetiracetam	•	Valproate products
•	Carbamazepine	•	Mesuximide	•	Zonisamide
•	Clobazam	•	Oxcarbazepine
•	Ethosuximide	•	Phenytoin

STK-001

The first potential disease-modifying approach to address the genetic cause of Dravet syndrome

Source: Lagae et al., Developmental Medicine & Child Neurology, 2017

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Landmark New Data Support the Potential for STK-001 to be The First Medicine to Treat the Underlying Cause of Dravet Syndrome

Reductions in seizures and improvements in cognition and behavior that support the potential for disease modification

Phase 1/2a Study Data: 70mg doses demonstrated substantial & sustained

reductions in convulsive seizure frequency of:

85% at		74% at
3 months	&	6 months

(n=10)(n=9)

on top of the best available anti-seizure medicines

OLE Studies (30mg, 45mg):
Clinically meaningful,
durable reductions in
seizures and improvements		Recent FDA clearance
in multiple measures of		for 3 doses of
cognition & behavior over		70mg and continued
12 months		dosing at 45mg

Next Steps: Meet with regulatory agencies to discuss

registrational study of 70mg followed by 45mg

OLE: Open-Label Extension Study

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