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tividenofusp alfa

Phase 2

Mucopolysaccharidosis II | Small molecule | Rare Disease |Denali Therapeutics Inc.|Last Updated: May 12, 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-BlindCONTROLLEDDMCBiomarker
Total Trials3
Total Enrollment209
FDA Designations
PRIORITY_REVIEWBREAKTHROUGH_THERAPYORPHAN_DRUGFAST_TRACK
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT06075537An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007PHASE2 ENROLLING BY_INVITATION 99Sep 20, 2023Jun 1, 2027May 12, 202627 United States, Argentina +11
NCT05371613A Study to Determine the Efficacy and Safety of Tividenofusp Alfa (DNL310) vs Idursulfase in Pediatric and Young Adult Participants With Neuronopathic (nMPS II) or Non-Neuronopathic Mucopolysaccharidosis Type II (nnMPS II)PHASE2 RECRUITING 63Jul 21, 2022Dec 1, 2027Aug 5, 202532 United States, Argentina +13
NCT04251026A Study of Tividenofusp Alfa (DNL310) in Pediatric Participants With Hunter SyndromePHASE1 ACTIVE NOT_RECRUITING 47Jul 16, 2020Feb 1, 2031Aug 7, 20257 United States, Canada +2
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Study Endpoints
Primary Endpoints
Incidence and intensity of treatment-emergent adverse events (TEAEs)
5 years
Clinically significant changes in urine total glycosaminoglycan (GAG) concentrations throughout the treatment period
5 years
Incidence and intensity of infusion-related reactions (IRRs)
5 years

The intensity of IRRs will be assessed following each infusion of DNL310 using the categories of Mild, Moderate and Severe. IRRs will be summarized overall as well as stratified by intensity.

Percent change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration (Cohort A)
24 weeks
Change from baseline in the Vineland Adaptive Behavior Scale, Third Edition (Vineland-3)(Cohort A)
96 weeks
Incidence and severity of treatment-emergent adverse events (TEAEs)
24 weeks, 104 weeks, and 357 weeks
Change from baseline in urine total glycosaminoglycan (GAG) concentrations
24 weeks, 104 weeks, and 357 weeks
Incidence and severity of infusion-related reactions (IRRs)
24 weeks, 104 weeks, and 357 weeks
Change from baseline in concomitant medications
24 weeks, 104 weeks, and 357 weeks
Secondary Endpoints
Percentage change from baseline in cerebrospinal fluid (CSF) heparan sulfate (HS) concentration
5 years
Change from baseline in the Vineland-3 Adaptive Behavior Scale
5 years
Change from baseline in the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) cognitive raw score
5 years
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Cohort A2EXPERIMENTALParticipants with nMPS II, aged ≥5 to ≤10 years
Cohort B2EXPERIMENTALParticipants with nMPS II or nnMPS II, aged ≥1 to ≤18 years
Cohort C2EXPERIMENTALParticipants with nMPS II, aged \<4 years
Cohort D2EXPERIMENTALParticipants with nMPS II or nnMPS II, aged ≤18 years with preexisting hepatomegaly who have never taken standard-of-care ERT
Cohort E2EXPERIMENTALParticipants with nMPS II, aged ≥6 years; participants with nnMPS II, aged \<6 or ≥17 years; or participants with nMPS II, aged ≥1 to ≤18 years, with a history of prior HSCT or gene therapy and have completed at least 48 weeks in Study DNLI-E-0001
Cohort A7EXPERIMENTALParticipants with nMPS II, aged ≥2 to \<6 years
Cohort B7EXPERIMENTALParticipants with nnMPS II, aged ≥6 to \<17 years
Cohort A: Participants with nMPS IIEXPERIMENTAL -
Cohort B: Participants with nnMPS IIEXPERIMENTAL -
Open-label Treatment PhaseEXPERIMENTALParticipants who meet pre-specified criteria may receive DNL310 or idursulfase
Cohort AEXPERIMENTALDose escalation followed by a consistent dose level in participants with neuronopathic MPS II
Cohort BEXPERIMENTALA consistent dose level in participants with non-neuronopathic MPS II, neuronopathic MPS II, or unknown phenotype followed by dose escalation in some participants.
Cohort CEXPERIMENTALA consistent dose level in participants with neuronopathic MPS II
Cohort DEXPERIMENTALA consistent dose level in participants with non-neuronopathic MPS II or neuronopathic MPS II
Cohort EEXPERIMENTALA consistent dose level in participants with non-neuronopathic MPS II or neuronopathic MPS II
Interventions
NameTypeDescription
tividenofusp alfaDRUGIntravenous repeating dose
idursulfaseDRUGIntravenous repeating dose
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Eligibility Criteria
Age RangeN/A — 18 Years
SexALL
Healthy VolunteersNo
Study Sites27

Key Inclusion Criteria: * For participants from Study DNLI-E-0002 only: Completed at least through the Week 49 visit in Study DNLI-E-0002 and did not discontinue study intervention early * For participants from Study DNLI-E-0007 only: Completed the treatment period of 96 weeks in Cohort A for nMPS ...

Countries:United StatesArgentinaBelgiumCanadaCzechiaFranceGermanyItalyNetherlandsSpainSwedenTurkey (Türkiye)United KingdomAustraliaBrazil
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Recent Changes (Last 90 Days)
LOWMay 26, 2026NCT05371613primaryCompletionDate: changed
LOWMay 26, 2026NCT06075537primaryCompletionDate: changed
LOWMay 26, 2026NCT04251026primaryCompletionDate: changed
LOWMay 24, 2026NCT05371613studyFirstPostDate: changed
LOWMay 24, 2026NCT06075537studyFirstPostDate: changed
LOWMay 24, 2026NCT04251026studyFirstPostDate: changed