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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): November 14, 2022

 

Stoke Therapeutics, Inc.

(Exact Name of Registrant as Specified in its Charter)

 

 

Delaware	001-38938	47-1144582
(State or other jurisdiction of incorporation or organization)	(Commission File Number)	(I.R.S. Employer Identification No.)

 

45 Wiggins Ave Bedford, Massachusetts	01730
(Address of principal executive offices)	(Zip Code)

 

Registrant’s telephone number, including area code: (781) 430-8200

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.0001 par value per share		STOK		Nasdaq Global Select Market

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

 

 

 

 

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Item 2.02 Results of Operations and Financial Condition.

 

On November 14, 2022, Stoke Therapeutics, Inc. (the “Company”) issued a press release announcing its financial results for the quarter ended September 30, 2022, and providing business updates, including certain key findings from an interim analysis of its ongoing MONARCH and ADMIRAL clinical studies. A copy of the press release is attached as Exhibit 99.1 to this report.

 

Item 7.01 Regulation FD.

 

On November 14, 2022, the Company will be hosting an investor presentation (the “Presentation”), which will include updates and certain key findings from an interim analysis of its ongoing MONARCH and ADMIRAL clinical studies. A copy of the Presentation deck is attached as Exhibit 99.2 to this report.

 

The information with this report, including Exhibits 99.1 and 99.2 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”). The information contained in this report, including Exhibits 99.1 and 99.2 to this report, shall not be incorporated by reference into any other filing under the Exchange Act or under the Securities Act, except as shall be expressly set forth by specific reference in such filing.

Item 9.01 Financial Statements and Exhibits.

(d)

Exhibits

 

Exhibit Number	Description
99.1	Press release issued by Stoke Therapeutics, Inc. regarding its Q3 2022 financial results, dated November 14, 2022
99.2	Presentation, dated as of November 14, 2022
104	Cover Page Interactive Data File (embedded within the Inline XBRL document)

 

 

2

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SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

		STOKE THERAPEUTICS, INC.
Date: November 14, 2022		By:	/s/ Stephen J. Tulipano
			Stephen J. Tulipano
			Chief Financial Officer

 

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Exhibit 99.1

Stoke Therapeutics Reports Third Quarter Financial Results and Provides Business Updates

 

– Company announces positive interim data from the ongoing Phase 1/2a clinical studies of STK-001 in children and adolescents with Dravet syndrome –

 

– Single and multiple doses of STK-001 up to 45mg were well-tolerated –

 

– 55% median reduction from baseline in convulsive seizure frequency was observed among patients treated with three doses of 45mg –

 

– In 2023 the Company plans to report data from more patients treated with multiple doses of 45mg as well as those treated with multiple doses of 70mg –

 

– As of September 30, 2022, Company had $252.2 million in cash, cash equivalents, marketable securities, and restricted cash, anticipated to fund operations into 2025 –

 

– Management will host a webinar and conference call for analysts and investors at 8:30 a.m. Eastern Time today –

 

BEDFORD, Mass., November 14, 2022 – Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to addressing the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines, today reported financial results for the third quarter of 2022 and provided business updates, including positive data from a planned interim analysis of the ongoing Phase 1/2a MONARCH and ADMIRAL clinical studies of STK-001 in children and adolescents with Dravet syndrome. In addition to positive safety, pharmacokinetic (PK) and cerebrospinal fluid (CSF) exposure data, median reductions in seizure frequency were observed among patients who were treated with multiple doses of STK-001 (20mg, 30mg and 45mg). Management will host a webinar and conference call today at 8:30 a.m. Eastern Time.

 

Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures beginning within the first year of life. Complications of the disease often contribute to poor quality of life for patients and their caregivers. Despite available anti-seizure medicines, seizures are not adequately controlled for more than 90% of patients. STK-001 is a proprietary antisense oligonucleotide (ASO) being developed by Stoke as the first potential new medicine to address the genetic cause of Dravet syndrome.

 

“We are encouraged by the data from our ongoing studies of STK-001, which continue to demonstrate favorable safety findings and reductions in seizure frequency among a highly refractory group of patients,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “Half of the patients in these studies were taking four or more anti-seizure medicines, including fenfluramine, setting a high bar for STK-001 to demonstrate additional benefit. Even so, 74% of patients experienced a reduction in seizure frequency following three doses of STK-001. Most notable is the 55% median reduction observed among the small group of patients treated with three doses of 45mg. Based on these data, we believe we have entered the

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therapeutic range, which is translating to a clinical benefit for patients. We look forward to additional data in 2023.”

 

Study Design

MONARCH and ADMIRAL are multi-center, Phase 1/2a studies of children and adolescents who have an established diagnosis of Dravet syndrome. The primary objectives for MONARCH in the United States and ADMIRAL in the United Kingdom are to assess the safety and tolerability of STK-001, as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective is to assess the efficacy of STK-001 as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency.

 

Key safety findings from the interim analysis include:

The interim safety analysis reported today was based on data from 55 patients who were treated with single or multiple doses of STK-001 (10mg, 20mg, 30mg, 45mg) and followed for up to six months after their last dose.  

 

 

Key efficacy findings from the interim analysis include:

The interim efficacy analysis was based on data from 27 patients who were treated with multiple doses (20mg, 30mg, 45mg) and followed for three months after their last dose.  

 

 

Key PK and CSF exposure findings:

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The Company expects to provide more detail on data from the ongoing clinical studies at the American Epilepsy Society annual meeting December 2-6, 2022 in Nashville, TN.

 

Stoke Webinar and Conference Call for Analysts and Investors

Stoke will host a webinar and conference call for analysts and investors at 8:30 a.m. Eastern Time on Monday, November 14, 2022, to present the interim data from the ongoing Phase 1/2a clinical studies of STK-001. To participate in the call, please dial (800) 715-9871, or (646) 307-1963 for international callers and provide conference call ID number 2168761. The webinar will be broadcast live on the Investors & Media section of Stoke’s website at https://investor.stoketherapeutics.com/and can be accessed by following this Link. An archived replay of the webinar will be available for at least 90 days following the event.

 

Third Quarter 2022 Business Highlights and Recent Developments

 

Third Quarter 2022 and Year-to-Date Financial Results

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About TANGO

TANGO (Targeted Augmentation of Nuclear Gene Output) is Stoke’s proprietary research platform. Stoke’s initial application for this technology are diseases in which one copy of a gene functions normally and the other is mutated, also called haploinsufficiencies. In these cases, the mutated gene does not produce its share of protein, resulting in disease. Using the TANGO approach and a deep understanding of RNA science, Stoke researchers design antisense oligonucleotides (ASOs) that bind to pre-mRNA and help the functional (or wild-type) genes produce more protein. TANGO aims to restore missing proteins by increasing – or stoking – protein output from healthy genes, thus compensating for the mutant copy of the gene.

 

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 intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. The disease is classified as a developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP. There are no approved disease-modifying therapies for people living with Dravet syndrome. One out of 16,000 babies are born with Dravet syndrome, which is not concentrated in a particular geographic area or ethnic group.

 

About STK-001

STK-001 is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing clinical trials. 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 Na_V1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological Na_V1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities.

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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 FDA and the EMA, and rare pediatric disease designation by the FDA as a potential new treatment for Dravet syndrome.

 

About Phase 1/2a MONARCH Study (United States)

The MONARCH study is a Phase 1/2a open-label study of children and adolescents ages 2 to 18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study are to assess the safety and tolerability of STK-001, as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective is to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Stoke also intends to measure non-seizure aspects of the disease, such as quality of life, as secondary endpoints. Additional information about the MONARCH study can be found at https://www.monarchstudy.com/.

 

Patients who participated in the MONARCH study and meet study entry criteria are eligible to continue treatment in SWALLOWTAIL, an open-label extension (OLE) study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001. We expect that SWALLOWTAIL will also provide valuable information on the preliminary effects of STK-001 on seizures along with non-seizure aspects of the disease, such as quality of life and cognition.

Enrollment and dosing in SWALLOWTAIL are underway.

 

About Phase 1/2a ADMIRAL Study (United Kingdom)

The ADMIRAL study is a Phase 1/2a open-label study of children and adolescents ages 2 to <18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study are to assess the safety and tolerability of multiple doses of STK-001, as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective is to assess the effect of multiple doses of STK-001 as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Stoke also intends to measure non-seizure aspects of the disease, such as overall clinical status and quality of life, as secondary endpoints. Additional information about the ADMIRAL study can be found at https://www.admiralstudy.com.

 

Patients who participated in the ADMIRAL study and meet study entry criteria are eligible to continue treatment in LONGWING, an open-label extension (OLE) study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001. We expect that LONGWING will also provide valuable information on the preliminary effects of STK-001 on seizures along with non-seizure aspects of the disease, such as quality of life and cognition.

Enrollment and dosing in LONGWING are underway.

 

About Autosomal Dominant Optic Atrophy (ADOA)

Autosomal dominant optic atrophy (ADOA) is the most common inherited optic nerve disorder. It is a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Severity can vary and the rate of vision loss can be difficult to predict. Roughly

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half of people with ADOA fail driving standards and up to 46% are registered as legally blind. More than 400 OPA1 mutations have been reported in people diagnosed with ADOA. Currently there is no approved treatment for people living with ADOA. ADOA affects approximately one in 30,000 people globally with a higher incidence in Denmark of one in 10,000 due to a founder effect.

 

About STK-002

STK-002 is a proprietary antisense oligonucleotide (ASO) in preclinical development for the treatment of Autosomal Dominant Optic Atrophy (ADOA). Approximately 80% of individuals with ADOA experience symptoms before age 10, typically beginning between the ages of 4 and 6.  Stoke believes that STK-002 has the potential to be the first disease-modifying therapy for people living with ADOA. An estimated 65% to 90% of cases are caused by mutations in the OPA1 gene, most of which lead to a haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation. STK-002 is designed to upregulate OPA1 protein expression by leveraging the non-mutant (wild-type) copy of the OPA1 gene to restore OPA1 protein expression with the aim to stop or slow vision loss in patients with ADOA. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-002. STK-002 has been granted orphan drug designation by the FDA as a potential new treatment for ADOA.

 

About the FALCON Study

FALCON is a multicenter, prospective natural history study of people ages 8 to 60 who have an established clinical diagnosis of ADOA that is caused by a heterozygous OPA1 gene variant. No investigational medications or other treatments will be provided. The study is expected to enroll approximately 45 patients across 10 sites in the U.S., U.K., Italy and Denmark. Patients will undergo assessments at 6 months, 12 months, 18 months, and 24 months. There will be no additional follow-up period. For more information about enrolling in the study, please email Falconstudy@medpace.com.

 

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to addressing the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore protein levels. Stoke’s first compound, STK-001, is in clinical testing for the treatment of Dravet syndrome, a severe and progressive genetic epilepsy. Dravet syndrome is one of many diseases caused by a haploinsufficiency, in which a loss of ~50% of normal protein levels leads to disease. Stoke is pursuing the development of STK-002 for the treatment of autosomal dominant optic atrophy (ADOA), the most common inherited optic nerve disorder. Stoke’s initial focus is haploinsufficiencies and diseases of the central nervous system and the eye, although proof of concept has been demonstrated in other organs, tissues, and systems, supporting its belief in the broad potential for its proprietary approach. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow Stoke on Twitter at @StokeTx. 

 

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Cautionary Note Regarding 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 Company’s quarterly results and cash runway; its future operating results, financial position and liquidity; the ability of STK-001 to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in non-seizure comorbidities; the ability of STK-002 to treat the underlying causes of ADOA; the timing and expected progress of clinical trials, data readouts and presentations; the timing or receipt of regulatory approvals; the ability of TANGO to design medicines to increase protein production and the expected benefits thereof. Statements including words such as “plan,” “will,” “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 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: the Company’s ability to advance its product candidates, obtain regulatory approval of and ultimately commercialize its product candidates; the timing and results of preclinical and clinical trials; the risk that 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 and preliminary interim data readouts of ongoing trials may show results that change when such trials are completed; the Company’s ability to fund development activities and achieve development goals; the Company’s ability to protect its intellectual property; the direct and indirect impacts of the ongoing COVID-19 pandemic and its variants on the Company’s business; and other risks and uncertainties described under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2021, its quarterly reports on Form 10-Q, and the other documents the Company files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

 

Stoke Media & Investor Contacts:

Dawn Kalmar

Chief Communications Officer

dkalmar@stoketherapeutics.com

781-303-8302

 

Eric Rojas

Vice President, Investor Relations

IR@stoketherapeutics.com

617-312-2754

Financial Tables Follow

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Stoke Therapeutics, Inc.

Condensed consolidated balance sheets

(in thousands, except share and per share amounts)

(unaudited)

 

 

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Stoke Therapeutics, Inc.

Condensed consolidated statements of operations and comprehensive loss

(in thousands, except share and per share amounts)

(unaudited)

 

 

Interim Analysis of STK-001 for the Treatment of Dravet Syndrome Stoke Therapeutics November 14, 2022 Exhibit 99.2

Agenda Introduction Eric Rojas, Head of Investor Relations Introductory Remarks Edward M. Kaye, M.D., Chief Executive Officer Phase 1/2a Interim Analysis  Barry Ticho, M.D., Ph.D., Chief Medical Officer Closing Remarks Edward M. Kaye, M.D., Chief Executive Officer Q&A

Forward Looking Statements This presentation has been prepared by Stoke Therapeutics, Inc. (“Stoke” or “our”) 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 Dravet syndrome and reduce seizures or show improvements in non-seizure comorbidities, the timing and expected progress of clinical trials, data readouts, milestones and presentations, and the timing or receipt of regulatory approval. These forward-looking statements may be accompanied by such words as “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “likely,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. 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 the company’s 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 advance its product candidates, obtain regulatory approval of and ultimately commercialize its product candidates, the timing and results of preclinical and clinical trials, preliminary interim data readouts of ongoing trials showing results that change when such trials are completed, the company’s ability to fund development activities and achieve development goals, the company’s ability to protect intellectual property and other risks and uncertainties described under the heading “Risk Factors” in the Company's Annual Report on Form 10-K for the year ended December 31, 2021, its Quarterly Reports on Form 10-Q, and other documents the company files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this presentation, and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. These statements are based on our current beliefs and expectations and speak only as of the date of this presentation. We do not undertake any obligation to publicly update any forward-looking statements. 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.

Introductory Remarks Edward M. Kaye, M.D. Chief Executive Officer​

1 Sudden Unexpected Death in Epilepsy Sources: 2018 Health Advances Report; Djémié et al., Molecular Genetics & Genomic Medicine, 2016; Lagae et al., Developmental Medicine & Child Neurology, 2017; Nabbout et al., Orphanet Journal of Rare Diseases, 2013 ~35,000 Seizures are not adequately controlled in 90% of people with Dravet syndrome 85% of cases caused by a HAPLOINSUFFICIENCY of the SCN1A gene 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 50% NaV1.1 protein expression RESULTING in Dravet Syndrome: A Severe, Progressive Genetic Epilepsy

Non-Seizure Comorbidities of Dravet Syndrome Are Not Addressed by Current Therapies No Approved Disease-Modifying Therapies for Dravet Syndrome Intellectual disability Developmental delays Movement and balance issues Language and speech disturbances Growth defects Sleep abnormalities Disruptions of the autonomic nervous system Mood disorders Dravet syndrome is classified as a developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease

* VABS = Vineland Adaptive Behavior Scales * ABC score based on Communication, Daily Living, and Socialization domains and expressed relative to normative mean of 100 Source: BUTTERFLY: An Observational Study to Investigate Cognition and Other Non-seizure Comorbidities in Children and Adolescents with Dravet Syndrome (DS) (AES 2021). Initial findings showed: Validation of standard cognitive measures for use in DS patients Substantially decreased neurocognitive abilities despite the use of multiple anti-seizure medications A gap in adaptive functioning was observed in VABS* testing Gap in overall intellectual development and adaptive function between patients and neurotypical children appears to widen with age (n=36, 2-18 year-olds). Study ongoing. Non-Seizure Comorbidities of DS are Progressive and Measurable 100 80 60 40 20 0 24 48 72 96 120 144 168 192 216 Standard Score Age (m) Adaptive Behavior Composite (ABC)* Results from the VABS Assessment

Boldly Restoring Genetic Health Addressing the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines Executing in the clinic with STK-001, the first potential disease-modifying approach for the treatment of Dravet syndrome Advancing to the clinic with STK-002, the first potential disease-modifying approach for the treatment of Autosomal Dominant Optic Atrophy (ADOA) Expanding our pipeline through internal discovery and collaboration

Interim Analysis of Phase 1/2a MONARCH and ADMIRAL Studies of STK-001 Barry Ticho, M.D., Ph.D. Chief Medical Officer​

Nonsense mediated decay (NMD) exon without TANGO-ASO Increased functional protein expression Nonsense mediated decay (NMD) exon with TANGO-ASO NMD: nonsense-mediated decay

Clinical Study Designs: MONARCH SAD, MAD and ADMIRAL MAD

Demographics for 55 Patients Treated With >1 Dose of STK-001 Enrolled Patients Have Severe Disease and are Refractory to Standard Treatments   *N=45

Multiple Doses of STK-001 up to 45mg Well-Tolerated 27% (15/55) of patients experienced a TEAE related to study drug; All AEs related to study drug were mild or moderate  22% (12/55) of patients had a treatment-emergent SAE none related to study drug Most common TEAEs were vomiting, headache, and seizure 33% (18/55) of patients experienced CSF protein elevation (>50mg/dL) after dosing; no clinical manifestations were observed No new significant neurologic exam findings or lower extremity weakness emerged related to study drug All Adverse Events Related to Study Drug Were Mild or Moderate Data Cut-off date: August 11, 2022

Dose-Dependent Increases in Cmax and AUC24hr Observed in Plasma A greater increase was observed between 30mg and 45mg than between 20mg and 30mg Data Cut-off date: April 26, 2022

CSF Exposure was Measurable up to Six Months Following Multiple Doses of STK-001 in MONARCH study Slight increases in CSF values were observed from 20mg to 30mg Data Cut-off date: April 27, 2022

Majority of Patients Treated with Multiple Doses (20mg or 30mg) in MONARCH Reach Pharmacologically Active Brain Levels Clinical Data for 20mg and 30mg MAD Align with Model Simulations from Patient CSF Levels Solid line: Median of the predicted concentrations, Shaded area: 95th confidence interval (2.5th – 97.5th percentile) of the predicted concentrations, Open squares: Extrapolated concentrations. The 20mg MAD and 30mg MAD plots are for STK-001-DS-101 study. On Y axis, the dashed black lines indicate pharmacologically active concentration range Mean Brain without thalamus Pharmacologically active range Data Cut-off date: April 27, 2022

55% Median Reduction in Convulsive Seizure Frequency Observed in Patients Treated With Three Doses of STK-001 (45mg) Across the multiple dose cohorts (20mg, 30mg, 45mg), 74% (20/27) of patients experienced reductions in seizures Similar seizure reduction was observed among patients taking or not taking concomitant fenfluramine (>50% of patients were taking concomitant fenfluramine)

Reductions in Convulsive Seizure Frequency Observed Across Age Groups Seizure reductions more evident among patients ages 2-12

Phase 1/2a Trials of STK-001 for Dravet Syndrome are Ongoing Design Enrollment and dosing ongoing (30mg) Enrollment and dosing ongoing (45mg) Change in seizure frequency, overall clinical status, and quality of life Parallel studies in the US & UK evaluating children and adolescents ages 2 to 18 years old Evaluation of STK-001 (up to 45mg*) Evaluation of STK-001 (up to 70mg) Primary Endpoint Secondary Endpoint Open-Label Extension Safety and tolerability of SAD and MAD dose levels Safety and tolerability of MAD dose levels MAD @45mg: Dosing ongoing Status MAD @70mg: Dosing ongoing *Doses >45mg remain on FDA partial clinical hold Sources: Interim Safety, PK, and CSF Exposure Data from the Phase 1/2a MONARCH Study of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Dravet Syndrome (AES 2021). ADMIRAL: A UK Study of the Safety and Pharmacokinetics of Antisense Oligonucleotide STK-001 in Children and Adolescents with Dravet Syndrome (AES 2021) Characterize human pharmacokinetics (PK) and cerebrospinal fluid (CSF) drug exposure

Early Indication of Improvements in Non-Seizure Comorbidities as Measured by BRIEF-P* *Behavior Rating Inventory of Executive Function–Preschool Version, an assessment of pediatric executive function

Conclusions and Next Steps STK-001 on track as the first potential disease-modifying treatment for Dravet syndrome Multiple doses of STK-001 up to 45mg were well-tolerated Majority of patients treated with multiple doses of STK-001 experienced a reduction in seizures The effects were more pronounced at higher doses and among younger patients Continued progress toward identifying optimal dose level and frequency with dose-dependent responses observed between 30mg and 45mg Phase 1/2a studies ongoing, including an expanded 45mg MAD cohort in MONARCH and dosing in the 70mg MAD cohort in ADMIRAL. Expansion of 70mg cohort planned, pending safety review. Preliminary analysis from a small cohort of patients in SWALLOWTAIL (30mg) showed reductions in seizure frequency were maintained and an early indication of improvements in non-seizure comorbidities as measured by BRIEF-P Additional data anticipated in 2023 from the 45mg and 70mg multiple dose cohorts

Closing Remarks Edward M. Kaye, M.D. Chief Executive Officer​

Acknowledgements

Q&A