Stoke Therapeutics Declares Landmark New Information That Help the Potential for STK-001 to be the First Illness-Modifying Drugs for the Remedy of Sufferers with Dravet Syndrome

– Section 1/2a Finish of Research Information: 70mg doses demonstrated substantial and sustained reductions in convulsive seizure frequency on prime of the very best accessible anti-seizure medicines; Median reductions of 85% (n=10) at 3 months and 74% (n=9) at 6 months after final dose –

– Open Label Extension Research: Sturdy reductions in seizures and clinically significant enhancements in a number of measures of cognition and conduct have been maintained over 12 months with continued dosing at 30mg and 45mg –

– STK-001 usually well-tolerated –

– Firm to satisfy with regulatory businesses to debate registrational examine design with preliminary doses of 70mg adopted by continued dosing at 45mg –

– Webcast and convention name for analysts and traders at 4:30 p.m. Japanese Time right this moment –

BEDFORD, Mass.–(BUSINESS WIRE)–Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology firm devoted to addressing the underlying explanation for extreme illnesses by upregulating protein expression with RNA-based medicines, right this moment introduced landmark new information from two open-label Section 1/2a research and two open-label extension (OLE) research of youngsters and adolescents ages 2 to 18 with Dravet syndrome who have been handled with STK-001. Information from these research confirmed clinically significant results, together with substantial and sturdy reductions in convulsive seizure frequency and enhancements in a number of measures of cognition and conduct that help the potential for illness modification. These enhancements have been noticed amongst a extremely refractory group of sufferers who have been already taking the very best accessible anti-seizure medicines. STK-001 has been usually well-tolerated in research up to now.

In the present day, the Firm additionally introduced clearance from the U.S. Meals and Drug Administration (FDA) that enables sufferers to obtain three doses of 70mg adopted by continued dosing at 45mg. Primarily based on this regulatory replace and these information, the Firm plans to satisfy with regulatory businesses to debate a registrational examine that features preliminary doses of 70mg adopted by continued dosing at 45mg.

“The totality of those information present compelling proof that help the potential for STK-001 to be a disease-modifying medication for sufferers with Dravet syndrome by treating the underlying explanation for the illness, moderately than simply the signs,” stated Edward M. Kaye, M.D., Chief Govt Officer of Stoke Therapeutics. “STK-001 is the primary medication in improvement to display substantial and sturdy reductions in seizure frequency and enhancements in a number of measures of cognition and conduct. These results have been noticed in sufferers who have been already taking the very best accessible anti-seizure medicines, which confirms our extremely differentiated mechanism of motion and strategy to treating this illness. We look ahead to assembly with regulatory businesses to debate our plans for a randomized, managed registrational examine and to offering an replace popping out of these discussions later in 2024.”

“For many years, the first objective of treating Dravet syndrome has been to manage the frequency and severity of seizures, however, as we will now see from pure historical past information, many sufferers nonetheless expertise excessive charges of seizure frequency and fall additional and additional behind of their neurodevelopment,” stated Joseph Sullivan, M.D., FAES, Professor of Neurology and Pediatrics and Director of the Pediatric Epilepsy Middle of Excellence on the College of California San Francisco, and a distinguished researcher in Dravet syndrome. “A 50% discount in seizures is a vital measure of scientific efficacy, so an 80% discount on prime of any profit sufferers might already be getting from their baseline anti-seizure routine is profound. The additional proof of enhancements in expertise like communication, conduct, socialization and motion distinguish this strategy from something we’ve got seen up to now and mark our entry into a brand new period within the therapy of Dravet syndrome.”

Section 1/2a Research Outcomes: Substantial and Sustained Reductions in Convulsive Seizure Frequency

The Section 1/2a research have been multi-center and included youngsters and adolescents who’ve a longtime prognosis of Dravet syndrome. Sufferers enrolled in these research have been extremely refractory to therapy and taking the very best accessible anti-seizure medicines: 85% of sufferers have been taking not less than three and 54% have been taking not less than 4 medicines to manage seizures. Half the sufferers within the research have been taking concomitant fenfluramine.

New information from a mixed evaluation of 19 clinically evaluable sufferers who have been handled with one, two or three doses of 70mg demonstrated substantial reductions in convulsive seizure frequency in comparison with baseline at 3 months and at 6 months after the final dose, one among a number of secondary endpoints in every examine.

Noticed Reductions in Convulsive Seizure Frequency Amongst Sufferers Handled with 70mg Doses of STK-001 within the Section 1/2a Research

^*Seizure information excluded from month 5-6 for 1 affected person as a result of >50% seizure diary was lacking

^†Seizure information excluded for two sufferers (1 affected person previous to 3m after final dose, 1 previous to 6m after final dose) following a change in background anti-seizure medicines

Open Label Extension Research: Sturdy reductions in seizures and clinically significant enhancements in a number of measures of cognition and conduct over 12 months with continued dosing at 30mg and 45mg

Eligible sufferers who accomplished therapy within the Section 1/2a research continued therapy with STK-001 in one among two OLEs. On the time of the evaluation, 92% (68/74) of eligible sufferers had enrolled within the OLEs and 84% (57/68) remained within the research.

Sturdy reductions in convulsive seizure frequency have been noticed all through the course of therapy. This evaluation solely included sufferers who acquired >30mg of STK-001 within the Section 1/2a research after which continued therapy with STK-001 (30mg or 45mg) each 4 months within the OLEs. Clinically significant enhancements from baseline by 12 months have been noticed in a number of measures of cognition and conduct, together with a number of sub-domains of the Vineland Adaptive Conduct Scale (VINELAND-3).

These enhancements are in stark distinction to current pure historical past examine information that confirmed that, on common, sufferers with Dravet syndrome skilled no significant enchancment in convulsive seizure frequency and exhibited widening gaps in cognition and conduct in comparison with neurotypical friends, regardless of therapy with the very best accessible anti-seizure medicines.

Key Security Findings

On the time of the analyses, 81 sufferers had been handled with STK-001. Security findings are summarized beneath.

• STK-001 was usually well-tolerated throughout the Section 1/2a and OLE research.
• Within the Section 1/2a research:
  • 30% (24/81) of sufferers skilled a treatment-emergent opposed occasion (TEAE) that was associated to review drug. The most typical have been CSF protein elevations and procedural vomiting; and
  • 22% (18/81) of sufferers had a treatment-emergent critical opposed occasion. These occasions have been assessed as unrelated to review drug aside from the beforehand reported case of 1 affected person who skilled Suspected Sudden Severe Antagonistic Reactions (SUSARs).
• A better incidence of CSF protein elevation was noticed within the OLEs. 74% (50/68) of sufferers within the OLEs had not less than 1 CSF protein worth >50 mg/dL. No scientific manifestations have been noticed in these sufferers.
• Throughout the research, one affected person discontinued therapy on account of examine drug. As beforehand reported, this affected person discontinued therapy within the OLE on account of elevated CSF protein.

Stoke Webcast and Convention Name for Analysts and Traders

Stoke will host a webcast and convention name for analysts and traders at 4:30 p.m. Japanese Time on March 25, 2024, to current landmark new information from two Section 1/2a research and two ongoing open-label extension (OLE) research in youngsters and adolescents ages 2 to 18 with Dravet syndrome. The webcast will likely be broadcast stay on the Traders & Information part of Stoke’s web site at https://investor.stoketherapeutics.com/. Contributors who wish to be part of the decision and ask a query might register right here to obtain the dial-in numbers and distinctive PIN to seamlessly entry the decision. In any other case please entry the listen-only webcast by clicking right here. An archived replay of the webcast will likely be accessible for not less than 90 days following the occasion.

About Dravet Syndrome

Dravet syndrome is a extreme and progressive genetic epilepsy characterised by frequent, extended and refractory seizures, starting throughout the first yr of life. Dravet syndrome is troublesome to deal with and has a poor long-term prognosis. Problems of the illness usually contribute to a poor high quality of life for sufferers and their caregivers. The consequences of the illness transcend seizures and infrequently embody mental incapacity, developmental delays, motion and steadiness points, language and speech disturbances, development defects, sleep abnormalities, disruptions of the autonomic nervous system and temper issues. The illness is assessed as a developmental and epileptic encephalopathy as a result of developmental delays and cognitive impairment related to the illness. In contrast with the final epilepsy inhabitants, folks residing with Dravet syndrome have the next threat of sudden sudden dying in epilepsy, or SUDEP. There are not any authorised disease-modifying therapies for folks residing with Dravet syndrome. One out of 16,000 infants are born with Dravet syndrome, which isn’t concentrated in a specific geographic space or ethnic group.

About STK-001

STK-001 is an investigational new medication for the therapy of Dravet syndrome at the moment being evaluated in ongoing scientific trials. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the primary disease-modifying remedy to handle the genetic explanation for 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 revive physiological NaV1.1 ranges, thereby lowering each prevalence of seizures and important non-seizure comorbidities. STK-001 has been granted orphan drug designation by the FDA and the EMA, and uncommon pediatric illness designation by the FDA as a possible new therapy for Dravet syndrome.

Concerning the U.S. Research: MONARCH (Section 1/2a) and SWALLOWTAIL (OLE)

The MONARCH examine was a Section 1/2a open-label examine of youngsters and adolescents ages 2 to 18 who’ve a longtime prognosis of Dravet syndrome and have proof of a genetic mutation within the SCN1A gene. The first aims for the examine have been to evaluate the security and tolerability of STK-001, in addition to to find out the pharmacokinetics in plasma and publicity in cerebrospinal fluid. A secondary goal was to evaluate the efficacy as an adjunctive antiepileptic therapy with respect to the proportion change from baseline in convulsive seizure frequency.

Following completion of MONARCH, sufferers who met examine entry standards have been eligible to proceed therapy in SWALLOWTAIL, an open-label extension (OLE) examine designed to guage the long-term security and tolerability of repeat doses of STK-001. The examine can also be evaluating the long-term results of STK-001 on convulsive seizure frequency and on conduct, cognition and general high quality of life. Dosing in SWALLOWTAIL is ongoing.

Concerning the UK Research: ADMIRAL (Section 1/2a) and LONGWING (OLE)

The ADMIRAL examine was a Section 1/2a open-label examine of youngsters and adolescents ages 2 to <18 who’ve a longtime prognosis of Dravet syndrome and have proof of a genetic mutation within the SCN1A gene. The first aims for the examine have been to evaluate the security and tolerability of a number of doses of STK-001, in addition to to find out the pharmacokinetics in plasma and publicity in cerebrospinal fluid. A secondary goal was to evaluate the impact of a number of doses of STK-001 as an adjunctive antiepileptic therapy with respect to the proportion change from baseline in convulsive seizure frequency. Total scientific standing and high quality of life have been secondary endpoints of ADMIRAL.

Following completion of ADMIRAL, sufferers who met examine entry standards have been eligible to proceed therapy in LONGWING, an open-label extension (OLE) examine designed to guage the long-term security and tolerability of repeat doses of STK-001. The examine can also be evaluating the long-term results of STK-001 on convulsive seizure frequency and on conduct, cognition and general high quality of life. Dosing in LONGWING is ongoing.

Concerning the BUTTERFLY Observational Research

The BUTTERFLY examine was a multicenter, longitudinal, potential, observational examine of youngsters and adolescents ages 2 to 18 who’ve been recognized with Dravet syndrome because of an SCN1A gene mutation. This examine was designed to guage neurodevelopmental standing and alter from baseline to 24 months. Secondary and exploratory endpoints within the examine evaluated adjustments in different illness measures, together with seizures and extra non-seizure comorbidities. No investigational medicines or different therapies have been supplied. Contributors continued to obtain their common care, together with anti-seizure medicines, and have been noticed for as much as two years. The examine was performed at roughly 20 websites in america. Two-year outcomes have been introduced on the American Epilepsy Society in December 2023 and confirmed that, on common, sufferers skilled no significant enchancment in convulsive seizure frequency and exhibited widening gaps in cognition and conduct in comparison with neurotypical friends, regardless of therapy with the very best accessible anti-seizure medicines.

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK), is a biotechnology firm devoted to addressing the underlying explanation for extreme illnesses by upregulating protein expression with RNA-based medicines. Utilizing Stoke’s proprietary TANGO (Focused Augmentation of Nuclear Gene Output) strategy, Stoke is growing antisense oligonucleotides (ASOs) to selectively restore protein ranges. Stoke’s first compound, STK-001, is in scientific testing for the therapy of Dravet syndrome, a extreme and progressive genetic epilepsy. Dravet syndrome is one among many illnesses brought on by a haploinsufficiency, wherein a lack of ~50% of regular protein ranges results in illness. Stoke is pursuing the event of STK-002 for the therapy of autosomal dominant optic atrophy (ADOA), the commonest inherited optic nerve dysfunction. Stoke’s preliminary focus is haploinsufficiencies and illnesses of the central nervous system and the attention, though proof of idea has been demonstrated in different organs, tissues, and programs, supporting its perception within the broad potential for its proprietary strategy. Stoke is headquartered in Bedford, Massachusetts with places of work in Cambridge, Massachusetts. For extra info, go to https://www.stoketherapeutics.com/.

Cautionary Word Relating to Ahead-Wanting Statements

This press launch comprises forward-looking statements throughout the which means of the “protected harbor” provisions of the Personal Securities Litigation Reform Act of 1995, together with, however not restricted to, the power of STK-001 to deal with the underlying causes of Dravet syndrome and cut back seizures or present enhancements in conduct and cognition on the indicated dosing ranges or in any respect, and the timing and anticipated progress of scientific trials, information readouts, regulatory conferences, regulatory selections and different displays. Statements together with phrases corresponding to “count on,” “plan,” “will,” “proceed,” or “ongoing” and statements sooner or later tense are forward-looking statements. These forward-looking statements contain dangers and uncertainties, in addition to assumptions, which, in the event that they show incorrect or don’t absolutely materialize, might trigger our outcomes to vary materially from these expressed or implied by such forward-looking statements, together with, however not restricted to, dangers and uncertainties associated to: the Firm’s potential to advance, get hold of regulatory approval of, and finally commercialize its product candidates, together with STK-001; the timing of knowledge readouts and interim and ultimate outcomes of preclinical and scientific trials; the receipt and timing of potential regulatory selections; constructive ends in a scientific trial might not be replicated in subsequent trials or successes in early stage scientific trials might not be predictive of ends in later stage trials; the Firm’s potential to fund improvement actions and obtain improvement targets into 2025; the Firm’s potential to guard its mental property; the direct or oblique affect of world enterprise, political and macroeconomic circumstances, together with inflation, rate of interest volatility, cybersecurity occasions, uncertainty with respect to the federal finances, instability within the world banking system and risky market circumstances, and world occasions, together with public well being crises, and ongoing geopolitical conflicts, such because the conflicts in Ukraine and the Center East; and different dangers and uncertainties described below the heading “Threat Elements” within the Firm’s Annual Report on Kind 10-Okay for the yr ended December 31, 2023, its quarterly experiences on Kind 10-Q, and the opposite paperwork it information occasionally with the Securities and Alternate Fee. These forward-looking statements communicate solely as of the date of this press launch, and the Firm undertakes no obligation to revise or replace any forward-looking statements to mirror occasions or circumstances after the date hereof.

Contacts

Stoke Media & Investor Contacts:
Daybreak Kalmar

Chief Communications Officer

dkalmar@stoketherapeutics.com
781-303-8302

Eric Rojas

Vice President, Investor Relations

IR@stoketherapeutics.com
617-312-2754