Our Pipeline

This investigational RTM is being studied in FUSION, a Phase 1-3, multicenter, three-part study evaluating the pharmacokinetics, pharmacodynamics, efficacy, and safety of ulefnersen in up to 95 patients. Part 1 will consist of patients randomized in a 2:1 ratio to receive a multidose regimen of ulefnersen or placebo for a period of 
60 weeks, followed by part 2, in which patients will receive open-label ulefnersen for a period of 84 weeks. Patients may continue to receive open-label ulefnersen in part 3 for up to 3 additional years or until it becomes commercially available in the patient's country.^2,3

This investigational RTM is being assessed in a Phase 1-3, double-blind, placebo-controlled, multiple ascending-dose study evaluating the safety and efficacy of zilganersen in improving or stabilizing gross motor function across the affected domains in 73 patients with AxD. Patients will be randomized in a 2:1 ratio to receive zilganersen or matching placebo for a 60-week double-blind treatment period; then all patients will receive zilganersen for a 60-week open-label treatment period followed by a 120-week open-label, long-term extension period, and a 28-week posttreatment follow-up period.^3,4

Some study sites will include an optional open-label sub-study in patients <2 years of age.⁴

This investigational RTM is being assessed in HALOS, a Phase 1-2a, open-label, three-part study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses (MAD) of ION582 administered intrathecally (IT) in up to 55 patients with AS.^2,3
 
Part 1 of the study consists of a 13-week MAD treatment period, with a 12- to 32-week post-MAD follow-up period. Part 2 is a multicenter 49-week study where patients who completed part 1 will receive IT bolus doses of ION582 followed by a minimum 12-week follow-up period. Part 3 extends the treatment period for patients who completed part 2 for up to an additional 3 years followed by a 32-week post-long-term extension 
follow-up period.³

This investigational RTM is being studied in PrProfile, a Phase 1-2a, first-in-human, randomized, multicenter study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of intrathecally administered ION717 in approximately 56 patients with PrD. The study will consist of a screening period of up to 6 weeks, a 30-week double-blind treatment period, a 70-week open-label extension period, and a 32-week posttreatment period.^2,3 

This investigational RTM is being studied in ATTUNE, a Phase 1-2 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of intrathecally administered ION440 in pediatric and adult patients with MDS. This is a multicenter, two-part study with multiple dosing cohorts being evaluated in approximately 48 patients.^1,2
 
During part 1, patients will be randomized in a 3:1 ratio to receive ION440 or sham for 36 weeks. Patients who complete part 1 are eligible to enter part 2, an open-label, long-term extension study, where patients will receive ION440 for up to approximately 156 weeks.²

This RTM is being studied in ORBIT, a Phase 1b study to evaluate the safety, pharmacokinetics, and pharmacodynamics of intrathecally administered ION356 in male patients with PMD. This is a multicenter, multiple ascending-dose (MAD), multipart study enrolling approximately 24 pediatric patients.^2,3
 
The study will have two parts: a 48-week MAD part followed by an open-label, long-term extension (LTE) part of 109 weeks. During the MAD portion of the study, eligible patients will receive doses of ION356 and upon completion will transition to the open-label LTE to receive doses of ION356.³ 

This investigational RTM was evaluated in a Phase 1-2, randomized, double-blind, placebo-controlled study followed by an open-label extension to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of intrathecally administered IONIS-MAPTRx in patients with mild AD.^2,3

This investigational RTM is being studied in REASON, a Phase 1 study evaluating the safety, tolerability, and pharmacokinetics of single and multiple doses of ION859 administered via intrathecal injection in patients with PD. This is a randomized, blinded, placebo-controlled, multiple ascending-dose study open to patients with PD with verified presence or absence of variation in the leucine-rich repeat kinase 2 gene (LRRK2), but also to patients without any verified PD-related genetic variant.^2,3

This investigational RTM is being assessed in HORIZON, a Phase 1, multiple-ascending-dose (MAD) study (Part 1) to evaluate the safety, tolerability, PK, and PD of ION464 in adult participants diagnosed with MSA with a long-term extension (LTE) (Part 2). This is a first-in-human, randomized, blinded, placebo-controlled, multiple ascending-dose study of approximately 40 patients.^2,3

Part 1 of the study will consist of a screening period of up to 6 weeks, a treatment period of 12 weeks, and a follow-up period of 24 weeks. The study duration for each patient in part 2 will be approximately 96 weeks, consisting of a 72-week treatment period and a 24-week follow-up period.³

This investigational RTM is being studied in a Phase 1, randomized, blinded, placebo-controlled, single 
ascending-dose study in healthy adult male volunteers and an open-label multiple ascending-dose study in pediatric patients with SMA previously treated with onasemnogene abeparvovec. This study will evaluate the safety, tolerability, and pharmacokinetics of ION306.^2,3
 
Part 1 consists of screening, treatment, and follow-up periods that will last for 13 months. Part 2 will consist of a treatment and follow-up period for children with SMA and will last for 25 months.³

This investigational RTM is being studied in GENERATION HD2, a Phase 2 randomized, double-blind, placebo-controlled, dose-finding study to evaluate the safety, biomarkers, and efficacy of tominersen in patients with prodromal and early manifest HD.^2,3