Slide 1: Relutrigine: EMBOLD Phase 2 Study Topline Results
RELUTRIGINE: EMBOLD Phase 2 Study Topline Results September 3, 2024 ®
Slide 2: Forward-looking statements
2 Forward-looking statements This presentation may contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and financial conditions, including but not limited to express or implied statements regarding the
Slide 3: Relutrigine - EMBOLD delivers unparalleled results in DEE
3 Relutrigine - EMBOLD delivers unparalleled results in DEE 46% placebo-adjusted seizure reduction Unprecedented level of seizure freedom 5 patients seizure-free for longer than 28 days Well-tolerated in a heavily treated population 75% long-term median seizure reduction Disease modifying impact for
Slide 4: >$500M US Market Opportunity
4 >$500M US Market Opportunity * Poke G, Stanley J, Scheffer IE, Sadleir LG. Epidemiology of Developmental and Epileptic Encephalopathy and of Intellectual Disability and Epilepsy in Children >100k Developmental Epilepsies with high seizure burden using sodium channel blockers* >$2B+ Opportunity for
Slide 5: Disease Overview: Developmental and Epileptic Encephalopathies (DEEs)
5 Disease Overview: Developmental and Epileptic Encephalopathies (DEEs) RELUTRIGINE
Slide 6: DEEs are demanding and devastating with early mortality
6 DEEs are demanding and devastating with early mortality The incidence of DEE is expected to be 1/10,000 live births Characterized by frequent seizures, abnormal brain function, and developmental disability, typically beginning in infancy Often caused by mutations that disrupt function of brain vol
Slide 7: SCN2A and SCN8A are amongst the most severe and refractory forms of DEE
7 • SCN2A and SCN8A conditions are caused by mutations in ion channels that disrupt normal function • Patients with SCN2A and SCN8A DEEs frequently exhibit symptoms from birth, persisting their entire life, including: • Severe and uncontrollable early-onset seizures • Movement disorders • Pronounced
Slide 8: Relutrigine Mechanism of Action
8 RELUTRIGINE Mechanism of Action
Slide 9: Relutrigine potential first- and best-in-class small molecule for DEEs
9 Preclinical and emerging clinical data demonstrate relutrigine has the potential to be a first- and best-in-class small molecule for DEEs Superior selectivity for disease-state NaV channel hyperexcitability Convenient auto-titration regimen with stable PK Unprecedented therapeutic window with pote
Slide 10: Superior potency and selectivity for disease-state NaV channel hyperexcitability
10 % INHIBITION OF hNaV1.6 PERSISTENT INa COMPARISON OF POTENCY AND SELECTIVITY Superior potency and selectivity for disease-state NaV channel hyperexcitability 0.01 0.1 1 10 100 1000 10000 0 20 40 60 80 100 Concentration (µM) % Inhibition Carbamazepine Lamotrigine Cenobamate Relutrigine Persistent
Slide 11: Functional selectivity translates to a wide therapeutic index in vivo
11 MES EFFICACY sLMA TOLERABILITY Functional selectivity translates to a wide therapeutic index in vivo for relutrigine Therapeutic Index (TI) = TC50 / EC50 CD-1 mice; (n=12/group) **p<0.01 vs. Veh ED50: 2 mg/kg Molecule Plasma Therapeutic Index Relutrigine 16.2x Relutrigine (mg/kg, PO) Relutrigine
Slide 12: Relutrigine Topline Data
RELUTRIGINE Topline Data &} EmBoid
Slide 13: Relutrigine Phase 2 EMBOLD study design and endpoints
13 KEY ENDPOINTS: Incidence and severity of treatment-emergent adverse events (TEAEs) Change from baseline in monthly (28-day) motor seizure frequency Seizure freedom achieved for a 4-week period Clinical and Caregiver Global Impression of Improvement and Severity Relutrigine Phase 2 EMBOLD study de
Slide 14: EMBOLD study disposition
14 EMBOLD study disposition *Patients assigned to placebo received placebo for one (4 week) period and relutrigine for 3 periods **1 patient had no available data for efficacy assessment Assessed for eligibility (n=21) Did not meet inclusion criteria (n=5) Placebo (n=8)* • Safety population (n=8) •
Slide 15: Demographics and Baseline Characteristics
15 Demographics and Baseline Characteristics Placebo (n = 8) Total (n = 16) Age, mean (min, max) 6.1 (3, 12) 5.9 (2, 14) DEE SCN2A, n (%) 4 (50) 7 (44) SCN8A, n (%) 4 (50) 9 (56) Gender (Male / Female, %) 5/3 (63/37) 9/7 (56/44) Age at seizure onset (n) 0 – 3 months 7 13 4 – 12 months 1 2 >12 months
Slide 16: Relutrigine was generally well-tolerated
16 Relutrigine was generally well-tolerated *Infections include bronchiolitis, conjunctivitis, gastroenteritis, influenza, metapneumovirus infection, nasopharyngitis, otitis media, pneumonia, respiratory tract infection, rhinovirus infection scarlet fever, tonsillitis, upper respiratory tract infect
Slide 17: Robust reduction in motor seizures and unprecedented seizure-free status
17 Relutrigine demonstrated robust reduction in motor seizures and unprecedented seizure-free status per 28-day period *Percent reduction derived from log-transformed placebo-adjusted relutrigine effect **Assessment of motor seizures over the controlled plus open-label periods through August 21, 202
Slide 18: Significant short- and long-term improvement in motor seizures
18 -90% -80% -70% -60% -50% -40% -30% -20% -10% 0% Relutrigine patients demonstrated significant improvement over the short and long-term in motor seizures Long-term extension data for 8 patients with data available for at least one 28-day period as of August 21, 2024 Placebo (n=7) -1.6% Relutrigine
Slide 19: CGI-I and CgGI-I assessed at Week-16
Clinical Global Impression of Improvement and Caregiver Global Impression of Improvement assessed at Week-16 visit 19 57% 71% 43% 29% 69% 62% 31% 23% 0% 10% 20% 30% 40% 50% 60% 70% 80% Alertness Seizure Severity and Intensity Communication Disruptive Behavior Clinician Caregiver Relutrigine treatmen
Slide 20: Next Steps
20 Next Steps RELUTRIGINE
Slide 21: Relutrigine - EMBOLD delivers unparalleled results in DEE
21 Relutrigine - EMBOLD delivers unparalleled results in DEE 46% placebo-adjusted seizure reduction Unprecedented level of seizure freedom 5 patients seizure-free for longer than 28 days Well-tolerated in a heavily treated population 75% long-term median seizure reduction Disease modifying impact fo
Slide 22: SCN2A and SCN8A are the tip of the iceberg for other DEEs
22 SCN2A and SCN8A are the tip of the iceberg to address significant unmet need for other DEEs *Based PubMed Search of DEEs that could use SCBs to treat focal seizures when they presented. >$500m peak revenue Low tolerability and inadequate response >70% DEE patients treated with sodium channel bloc
Slide 23: Next steps: registrational cohort and EMERALD trial
23 Regulatory agency input • EMBOLD registrational Cohort 2 initiated • Leveraging EMBOLD successful study design Next steps Initiated registrational trial for SCN2A and 8A, discuss Other DEEs with FDA by Q1 2025 2H 2024 1H 2025 Initiate EMERALD Trial 1:1 Randomization N=80 (SCN2A/SCN8A) Relutrigine
Slide 24: Dare for More
- DARE FOR MORE