Stoke Therapeutics Presents Preclinical Data From Studies of STK-001 That Showed Improvements in Survival and Reductions in Seizure Frequency in a Mouse Model of Dravet Syndrome New data from electroencephalography (EEG)

Stoke Therapeutics Presents Preclinical Data From Studies of STK-001 That Showed Improvements in

Survival and Reductions in Seizure Frequency in a Mouse Model of Dravet Syndrome

New data from electroencephalography (EEG)

recordings showed 76% of Dravet syndrome (DS) mice treated with STK-001 were seizure free compared to 48% of placebo-treated mice

An 80% reduction in the average number of spontaneous seizures was also observed among treated DS mice

Data support the clinical development of STK-001 as a potential new medicine for Dravet syndrome, a

severe and progressive genetic epilepsy

BEDFORD, Mass., Dec. 7, 2019 - Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company

pioneering a new way to treat the underlying cause of severe genetic diseases by precisely upregulating protein expression, today announced preclinical data from studies of STK-001 that showed significant

improvements in survival and reductions in seizure frequency in a mouse model of Dravet syndrome (DS). New data from electroencephalography (EEG) recordings showed 76% (16/21) of DS mice treated with STK-001

were seizure free compared to 48% (10/21) that were treated with a placebo. An 80% reduction in the average number of spontaneous seizures (3 seizures vs 16 seizures) was also observed among treated DS mice compared to placebo. EEG is a highly

sensitive measure of seizure activity, which enables the detection of seizures that may not be otherwise visible. These data were presented in a poster session at the American Epilepsy Society (AES) Annual Meeting in Baltimore.

The data on STK-001 from this mouse model give us confidence in our approach to treating the underlying cause of

Dravet syndrome by restoring Nav1.1 protein expression to near normal levels, said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. The reductions in mortality previously observed with

STK-001 were compelling and the new EEG data provide further evidence of the potential for STK-001 to impact Dravet syndrome by reducing seizure frequency and possibly

preventing seizures entirely. What is particularly remarkable is that these data were generated from a spontaneous seizure model, which we believe accurately reflects the clinical situation in people with Dravet syndrome.

Dravet syndrome is a severe and progressive genetic epilepsy that begins within the first year of life. The effects of the disease go beyond seizures and

often include cognitive regression or developmental stagnation, ataxia, speech impairment and sleep disturbances. Approximately 85% of Dravet syndrome cases are caused by spontaneous, heterozygous variants in the SCN1A gene. This gene encodes

the voltage-gated sodium channel subunit, NaV1.1. STK-001 is a proprietary antisense oligonucleotide (ASO) designed to increase or upregulate protein production by manipulating the

cell s RNA splicing process.

In the studies presented in today s poster, the efficacy of STK-001 was

evaluated in a Scn1a-linked mouse model of Dravet syndrome that results in Nav1.1 haploinsufficiency. Seizures and Sudden Unexpected Death in Epilepsy (SUDEP) in these mice occurred spontaneously and were not provoked by temperature changes or other

manipulation. Mice were administered a single intracerebroventricular (ICV) injection of STK-001 or placebo at postnatal day 2 or postnatal day 14 and monitored to postnatal day 90. The data showed

improvements among mice treated with STK-001 compared to placebo, including:

Although we cannot make a direct correlation, these data are encouraging because they suggest a potential for

STK-001 to reduce seizure frequency in Dravet syndrome patients. Showing a 50% improvement in the number of DS mice that had no detectable seizures is a significant finding, particularly considering the high

seizure burden associated with Dravet syndrome, said Lori Isom, Ph.D., Maurice H. Seevers Professor and Chair of Pharmacology, University of Michigan Medical School. Across all measures, the data showed a consistent benefit for DS mice

treated with STK-001 compared to placebo, making the totality of these data compelling.

presentation are as follows:

Presentation Title: Targeted Augmentation of Nuclear Gene Output (TANGO) of Scn1a Prevents SUDEP in a Mouse

Model of Dravet Syndrome

Session Date & Time: Saturday, December 7, 2019, 12:00 p.m. 6:00 p.m. ET

Session Title: Poster Session 1

Isom, Ph.D., Maurice H. Seevers Professor and Chair of Pharmacology, University of Michigan Medical School

Location: The Baltimore Convention

Additional preclinical data will be presented on Sunday, December 8, 2019 showing biodistribution, target engagement,

pharmacodynamics, safety and tolerability in non-human primates treated with STK-001:

Presentation Title: TANGO Oligonucleotides for the Treatment of Dravet Syndrome: Safety, Biodistribution and Pharmacology in the Non-Human Primate

Session Date & Time: Sunday, December 8, 2019, 10:00 a.m. 4:00 p.m. ET

Session Title: Poster Session 2

Anne Christiansen, Ph.D., Associate Director, Neuroscience, Stoke Therapeutics

Poster Number: 2.195

Location: The Baltimore Convention Center, Hall E

posters for these studies will be made available online upon presentation at the meeting on the Events and Presentations section of Stoke s website at https://www.stoketherapeutics.com/.

STK-001 is an investigational new medicine for the treatment of Dravet syndrome. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential

to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to upregulate NaV1.1 protein expression by leveraging the

non-mutant (wild-type) copy of the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure

comorbidities. Stoke has generated preclinical data demonstrating proof-of-mechanism and

proof-of-concept for STK-001. STK-001 has been granted orphan drug designation by the

U.S. Food and Drug Administration as a potential new treatment for Dravet syndrome. Stoke plans to submit an investigational new drug application (IND) to the U.S. Food and Drug Administration in early 2020.

About Dravet Syndrome

Dravet syndrome is a severe and

progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of life. Dravet syndrome is difficult to treat and has a poor long-term

prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often include cognitive

regression or developmental stagnation, ataxia, speech impairment and sleep disturbances. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. Dravet

syndrome affects approximately 35,000 people in the United States, Canada, Japan, Germany, France and the United Kingdom, and it is not concentrated in a particular geographic area or ethnic group.

About Stoke Therapeutics

Stoke Therapeutics, Inc.

(Nasdaq: STOK), is a biotechnology company pioneering a new way to treat the underlying causes of severe genetic diseases by precisely upregulating protein expression to restore target proteins to near normal levels. Stoke aims to develop the first

precision medicine platform to target the underlying cause of a broad spectrum of genetic diseases in which the patient has one healthy copy of a gene and one mutated copy that fails to produce a protein essential to health. These diseases, in which

loss of approximately 50% of normal protein expression causes disease, are called autosomal dominant haploinsufficiencies. The company s lead investigational new medicine is STK-001, a proprietary

antisense oligonucleotide (ASO) that has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome, a severe and progressive genetic epilepsy. Stoke is headquartered in Bedford, Massachusetts with

offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow the company on Twitter at @StokeTx.

Forward-Looking Statements

This press release 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 improve survival and reduce seizure frequency in mice, as well as its biodistribution, target engagement and ability to increase protein expression in

non-human primates; our ability to use study data to advance the development of STK-001; the ability of STK-001 to treat the

underlying causes of Dravet syndrome; and the ability of TANGO to design medicines to increase protein production. Statements including words such as plan, continue, expect, or ongoing 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 do not fully materialize or prove incorrect, could cause our results to differ materially

from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause our actual activities or results to differ significantly from those expressed in any forward-looking

statement, including risks and uncertainties related to the company s ability to develop, obtain regulatory approval for and commercialize STK-001 and its future product candidates, the timing and results

of preclinical studies and clinical trials, the company s ability to protect intellectual property; and other risks set forth in our filings with the Securities and Exchange Commission, including the risks set forth in our quarterly report on

Form 10-Q for the three months ended September 30, 2019. These forward-looking statements speak only as of the date hereof and we specifically disclaim any obligation to update these forward-looking

statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.

Stoke Media & Investor Contact:

Vice President, Head of Corporate Affairs