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DNL593

Phase 1

Frontotemporal Dementia | Small molecule | Neurology |Denali Therapeutics Inc.|Last Updated: Jan 15, 2026

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment85
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT05262023A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia (FTD-GRN)PHASE1 ACTIVE NOT_RECRUITING 85Feb 1, 2022Nov 1, 2028Jan 15, 202626 United States, Belgium +10
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Study Endpoints
Primary Endpoints
Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs)
up to 18 months
Incidence of treatment-emergent clinically significant abnormalities in safety laboratory values
up to 18 months
Change from baseline in vital sign measurements: systolic and diastolic blood pressure
up to 18 months
Change from baseline in vital sign measurements: heart rate
up to 18 months
Change from baseline in vital sign measurements: respiratory rate
up to 18 months
Change from baseline in vital sign measurements: body temperature
up to 18 months
Change from baseline in electrocardiogram (ECG) results including PR, QRS, and QTcF intervals
up to 18 months
Incidence of treatment-emergent clinically significant abnormalities in physical/neurological examination findings
up to 18 months
Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS; Parts B and C only)
up to 18 months
Secondary Endpoints
PK Parameter: Maximum concentration (Cmax) of DNL593 in serum
up to 18 months
PK Parameter: Time to reach maximum concentration (tmax) of DNL593 in serum
up to 18 months
PK Parameter: Area under the concentration-time curve (AUC) from time zero to time of last measurable concentration (AUClast) of DNL593 in serum
up to 18 months
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
DNL593 (Healthy Participant)EXPERIMENTAL -
Placebo (Healthy Participant)PLACEBO_COMPARATOR -
DNL593 (Participants with FTD)EXPERIMENTAL -
Placebo (Participants with FTD)PLACEBO_COMPARATOR -
Interventions
NameTypeDescription
DNL593DRUGAscending single doses (for healthy participants) and multiple doses (for participants with FTD)
PlaceboDRUGAscending single doses (for healthy participants) and multiple doses (for participants with FTD)
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Eligibility Criteria
Age Range18 Years — 80 Years
SexALL
Healthy VolunteersYes
Study Sites26

Key Inclusion Criteria: Part A: * Women of non-childbearing potential (surgically sterilized or post menopausal) or men, aged ≥18 to ≤ 55 years * BMI of ≥ 18 to ≤ 32 kg/m² * When engaging in sex with a woman of child bearing potential, two forms of birth control are required Part B: * Women of n...

Countries:United StatesBelgiumBrazilColombiaCzechiaFranceItalyNetherlandsPortugalSpainTurkey (Türkiye)United Kingdom
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Recent Changes (Last 90 Days)
LOWMay 26, 2026NCT05262023primaryCompletionDate: changed
LOWMay 24, 2026NCT05262023studyFirstPostDate: changed